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Myelodysplastic syndromes

Abstract

Myelodysplastic syndromes (MDS) are a family of myeloid cancers with diverse genotypes and phenotypes characterized by ineffective haematopoiesis and risk of transformation to acute myeloid leukaemia (AML). Some epidemiological data indicate that MDS incidence is increasing in resource-rich regions but this is controversial. Most MDS cases are caused by randomly acquired somatic mutations. In some patients, the phenotype and/or genotype of MDS overlaps with that of bone marrow failure disorders such as aplastic anaemia, paroxysmal nocturnal haemoglobinuria (PNH) and AML. Prognostic systems, such as the revised International Prognostic Scoring System (IPSS-R), provide reasonably accurate predictions of survival at the population level. Therapeutic goals in individuals with lower-risk MDS include improving quality of life and minimizing erythrocyte and platelet transfusions. Therapeutic goals in people with higher-risk MDS include decreasing the risk of AML transformation and prolonging survival. Haematopoietic cell transplantation (HCT) can cure MDS, yet fewer than 10% of affected individuals receive this treatment. However, how, when and in which patients with HCT for MDS should be performed remains controversial, with some studies suggesting HCT is preferred in some individuals with higher-risk MDS. Advances in the understanding of MDS biology offer the prospect of new therapeutic approaches.

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Fig. 1: Epidemiology of MDS.
Fig. 2: Drivers of the development of aplastic anaemia, MDS and AML.
Fig. 3: Relationship between aplastic anaemia, MDS and AML.
Fig. 4: Frequent mutations affecting transcription, erythropoiesis, and DNA repair and conformation in MDS.
Fig. 5: Frequent mutations in RNA splicing, immune function and metabolism in MDS.
Fig. 6: Proposed algorithm for the treatment of MDS.
Fig. 7: Prognostic factors for different outcomes in intermediate-risk MDS.

References

  1. Cazzola, M. Myelodysplastic syndromes. N. Engl. J. Med. 383, 1358–1374 (2020). This review article discusses definitions, pathophysiology, diagnosis, risk stratification and therapy of MDS.

    Article  CAS  PubMed  Google Scholar 

  2. Bejar, R., Levine, R. & Ebert, B. L. Unraveling the molecular pathophysiology of myelodysplastic syndromes. J. Clin. Oncol. 29, 504–515 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Giagounidis, A. & Haase, D. Morphology, cytogenetics and classification of MDS. Best Pract. Res. Clin. Haematol. 26, 337–353 (2013).

    Article  CAS  PubMed  Google Scholar 

  4. Ma, X. Epidemiology of myelodysplastic syndromes. Am. J. Med. 125 (Suppl. 7), S2–S5 (2012). This review article discusses the epidemiology of MDS.

    Article  PubMed  PubMed Central  Google Scholar 

  5. National Cancer Institute. SEER Cancer Statistics Review, 1975-2016. Myelodysplastic Syndromes (MDS), Chronic Myeloproliferative Disorders (CMD), and Chronic Myelomonocytic Leukemia (CMML). National Cancer Institute http://seer.cancer.gov/csr/1975_2016/browse_csr.php?sectionSEL=30&pageSEL=sect_30_intro.01.html (2022).

  6. Offman, J. et al. Defective DNA mismatch repair in acute myeloid leukemia/myelodysplastic syndrome after organ transplantation. Blood 104, 822–828 (2004).

    Article  CAS  PubMed  Google Scholar 

  7. Garcia-Manero, G., Chien, K. S. & Montalban-Bravo, G. Myelodysplastic syndromes: 2021 update on diagnosis, risk stratification and management. Am. J. Hematol. 95, 1399–1420 (2020).

    Article  PubMed  Google Scholar 

  8. Goldberg, S. L. et al. Incidence and clinical complications of myelodysplastic syndromes among United States Medicare beneficiaries. J. Clin. Oncol. 28, 2847–2852 (2010).

    Article  PubMed  Google Scholar 

  9. Rollison, D. E. et al. Epidemiology of myelodysplastic syndromes and chronic myeloproliferative disorders in the United States, 2001-2004, using data from the NAACCR and SEER programs. Blood 112, 45–52 (2008).

    Article  CAS  PubMed  Google Scholar 

  10. Steensma, D. P. The changing classification of myelodysplastic syndromes: what’s in a name? Hematol. Am. Soc. Hematol. Educ. Program https://doi.org/10.1182/asheducation-2009.1.645 (2009).

    Article  Google Scholar 

  11. Khoury, J. D. et al. The 5th edition of the World Health Organization classification of haematolymphoid tumours: myeloid and histiocytic/dendritic neoplasms. Leukemia 36, 1703–1719 (2022). This publication is the fifth edition of the WHO Classification of MDS.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Valent, P. et al. Definitions and standards in the diagnosis and treatment of the myelodysplastic syndromes: consensus statements and report from a working conference. Leuk. Res. 31, 727–736 (2007).

    Article  PubMed  Google Scholar 

  13. Estey, E., Hasserjian, R. P. & Dohner, H. Distinguishing AML from MDS: a fixed blast percentage may no longer be optimal. Blood 139, 323–332 (2022). This article discusses how to distinguish MDS from AML.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Zeidan, A. M., Shallis, R. M., Wang, R., Davidoff, A. & Ma, X. Epidemiology of myelodysplastic syndromes: why characterizing the beast is a prerequisite to taming it. Blood Rev. 34, 1–15 (2019).

    Article  PubMed  Google Scholar 

  15. Slack, J., Nguyen, L., Naugler, C. & Rashid-Kolvear, F. Incidence of myelodysplastic syndromes in a major Canadian metropolitan area. J. Appl. Lab. Med. 3, 378–383 (2018).

    Article  PubMed  Google Scholar 

  16. Maynadie, M. et al. Epidemiological characteristics of myelodysplastic syndrome in a well-defined French population. Br. J. Cancer 74, 288–290 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Williamson, P. J., Kruger, A. R., Reynolds, P. J., Hamblin, T. J. & Oscier, D. G. Establishing the incidence of myelodysplastic syndrome. Br. J. Haematol. 87, 743–745 (1994).

    Article  CAS  PubMed  Google Scholar 

  18. Dinmohamed, A. G. et al. Trends in incidence, initial treatment and survival of myelodysplastic syndromes: a population-based study of 5144 patients diagnosed in the Netherlands from 2001 to 2010. Eur. J. Cancer 50, 1004–1012 (2014).

    Article  PubMed  Google Scholar 

  19. Gattermann, N. et al. Myelodysplastic syndromes: aspects of current medical care and economic considerations in Germany. Onkologie 31, 477–484 (2008).

    Article  PubMed  Google Scholar 

  20. Bonadies, N. et al. Trends of classification, incidence, mortality, and survival of MDS patients in Switzerland between 2001 and 2012. Cancer Epidemiol. 46, 85–92 (2017).

    Article  PubMed  Google Scholar 

  21. Avgerinou, C. et al. The incidence of myelodysplastic syndromes in Western Greece is increasing. Ann. Hematol. 92, 877–887 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  22. Moreno Berggren, D. et al. Prognostic scoring systems for myelodysplastic syndromes (MDS) in a population-based setting: a report from the Swedish MDS register. Br. J. Haematol. 181, 614–627 (2018).

    Article  PubMed  Google Scholar 

  23. Iglesias Gallego, M. et al. Incidence and characteristics of myelodysplastic syndromes in Ourense (Spain) between 1994–1998. Haematologica 88, 1197–1199 (2003).

    PubMed  Google Scholar 

  24. Gologan, R. Demo-geographical data of myelodysplastic syndrome based on a large sample of patients from a Romanian Hematological Center. J. BUON 15, 547–555 (2010).

    CAS  PubMed  Google Scholar 

  25. Semochkin, S., Tolstykh, T., Dudina, G. & Fink, O. Clinical and epidemiological characteristics of myelodysplastic syndromes in adults [Russian]. Georgian Med. News 252, 108–115 (2016).

    Google Scholar 

  26. Wang, W., Wang, H., Wang, X. Q. & Lin, G. W. First report of incidence of adult myelodysplastic syndrome in China. Ann. Hematol. 91, 1321–1322 (2012).

    Article  PubMed  Google Scholar 

  27. Park, E. H. et al. Nationwide statistical analysis of myeloid malignancies in Korea: incidence and survival rate from 1999 to 2012. Blood Res. 50, 204–217 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  28. Chihara, D. et al. Incidence of myelodysplastic syndrome in Japan. J. Epidemiol. 24, 469–473 (2014).

    Article  PubMed  Google Scholar 

  29. Rodger, E. J. & Morison, I. M. Myelodysplastic syndrome in New Zealand and Australia. Intern. Med. J. 42, 1235–1242 (2012).

    Article  CAS  PubMed  Google Scholar 

  30. Otrock, Z. K. et al. A nationwide non-interventional epidemiological data registry on myelodysplastic syndromes in Lebanon. Am. J. Blood Res. 5, 86–90 (2015).

    PubMed  PubMed Central  Google Scholar 

  31. Feliciano, S. V. M. et al. Incidence and mortality of myeloid malignancies in children, adolescents and young adults in Brazil: a population-based study. Cancer Epidemiol. 62, 101583 (2019).

    Article  PubMed  Google Scholar 

  32. Velez, A. et al. Incidence of myelodysplastic syndromes from a medical care program in Buenos Aires, Argentina. Clin. Lymphoma Myeloma Leuk. 19 (Suppl. 1), S346 (2019).

    Article  Google Scholar 

  33. Ma, X., Does, M., Raza, A. & Mayne, S. T. Myelodysplastic syndromes: incidence and survival in the United States. Cancer 109, 1536–1542 (2007).

    Article  PubMed  Google Scholar 

  34. Cronin, K. A., Ries, L. A. & Edwards, B. K. The surveillance, epidemiology, and end results (SEER) program of the National Cancer Institute. Cancer 120 (Suppl. 23), 3755–3757 (2014).

    Article  PubMed  Google Scholar 

  35. Craig, B. M., Rollison, D. E., List, A. F. & Cogle, C. R. Underreporting of myeloid malignancies by United States cancer registries. Cancer Epidemiol. Biomark. Prev. 21, 474–481 (2012).

    Article  Google Scholar 

  36. Cogle, C. R., Craig, B. M., Rollison, D. E. & List, A. F. Incidence of the myelodysplastic syndromes using a novel claims-based algorithm: high number of uncaptured cases by cancer registries. Blood 117, 7121–7125 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Cogle, C. R. et al. High rate of uncaptured myelodysplastic syndrome cases and an improved method of case ascertainment. Leuk. Res. 38, 71–75 (2014).

    Article  PubMed  Google Scholar 

  38. Sant, M. et al. Incidence of hematologic malignancies in Europe by morphologic subtype: results of the HAEMACARE project. Blood 116, 3724–3734 (2010).

    Article  CAS  PubMed  Google Scholar 

  39. Cogle, C. R. Incidence and burden of the myelodysplastic syndromes. Curr. Hematol. Malig. Rep. 10, 272–281 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  40. Niemeyer, C. M. & Baumann, I. Myelodysplastic syndrome in children and adolescents. Semin. Hematol. 45, 60–70 (2008).

    Article  CAS  PubMed  Google Scholar 

  41. Mian, S. A. & Bonnet, D. Nature or nurture? Role of the bone marrow microenvironment in the genesis and maintenance of Myelodysplastic syndromes. Cancers https://doi.org/10.3390/cancers13164116 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  42. Strom, S. S., Gu, Y., Gruschkus, S. K., Pierce, S. A. & Estey, E. H. Risk factors of myelodysplastic syndromes: a case-control study. Leukemia 19, 1912–1918 (2005).

    Article  CAS  PubMed  Google Scholar 

  43. Nisse, C. et al. Occupational and environmental risk factors of the myelodysplastic syndromes in the North of France. Br. J. Haematol. 112, 927–935 (2001).

    Article  CAS  PubMed  Google Scholar 

  44. Ma, X. et al. Obesity, lifestyle factors, and risk of myelodysplastic syndromes in a large US cohort. Am. J. Epidemiol. 169, 1492–1499 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  45. Morton, L. M. et al. Association of chemotherapy for solid tumors with development of therapy-related myelodysplastic syndrome or acute myeloid leukemia in the modern era. JAMA Oncol. 5, 318–325 (2019).

    Article  PubMed  Google Scholar 

  46. Advani, P. G. et al. Risk of therapy-related myelodysplastic syndrome/acute myeloid leukemia after childhood cancer: a population-based study. Leukemia 33, 2947–2978 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  47. Morton, L. M. et al. Risk of myeloid neoplasms after solid organ transplantation. Leukemia 28, 2317–2323 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Schnatter, A. R., Glass, D. C., Tang, G., Irons, R. D. & Rushton, L. Myelodysplastic syndrome and benzene exposure among petroleum workers: an international pooled analysis. J. Natl Cancer Inst. 104, 1724–1737 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Dalamaga, M. et al. Adiponectin and resistin are associated with risk for myelodysplastic syndrome, independently from the insulin-like growth factor-I (IGF-I) system. Eur. J. Cancer 44, 1744–1753 (2008).

    Article  CAS  PubMed  Google Scholar 

  50. Kim, S. Y. et al. Myelodysplastic syndrome evolving from aplastic anemia treated with immunosuppressive therapy: efficacy of hematopoietic stem cell transplantation. Haematologica 99, 1868–1875 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Sun, L. & Babushok, D. V. Secondary myelodysplastic syndrome and leukemia in acquired aplastic anemia and paroxysmal nocturnal hemoglobinuria. Blood 136, 36–49 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  52. Nakao, S. & Gale, R. P. Are mild/moderate acquired idiopathic aplastic anaemia and low-risk myelodysplastic syndrome one or two diseases or both and how should it/they be treated? Leukemia 30, 2127–2130 (2016). This paper presents ways to distinguish mild or moderate aplastic anaemia from low-risk MDS.

    Article  CAS  PubMed  Google Scholar 

  53. Polprasert, C. et al. Inherited and somatic defects in DDX41 in myeloid neoplasms. Cancer Cell 27, 658–670 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Avagyan, S. & Shimamura, A. Lessons from pediatric MDS: approaches to germline predisposition to hematologic malignancies. Front. Oncol. 12, 813149 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  55. Goyal, T., Tu, Z. J., Wang, Z. & Cook, J. R. Clinical and pathologic spectrum of DDX41-mutated hematolymphoid neoplasms. Am. J. Clin. Pathol. 156, 829–838 (2021).

    Article  CAS  PubMed  Google Scholar 

  56. Avgerinou, C. et al. Occupational, dietary, and other risk factors for myelodysplastic syndromes in Western Greece. Hematology 22, 419–429 (2017).

    Article  PubMed  Google Scholar 

  57. Babushok, D. V. A brief, but comprehensive, guide to clonal evolution in aplastic anemia. Hematol. Am. Soc. Hematol. Educ. Program 2018, 457–466 (2018).

    Article  Google Scholar 

  58. Mewawalla, P. & Dasanu, C. A. Immune alterations in untreated and treated myelodysplastic syndrome. Expert Opin. Drug Saf. 10, 351–361 (2011).

    Article  CAS  PubMed  Google Scholar 

  59. Beck, D. B. et al. Somatic mutations in UBA1 and severe adult-onset autoinflammatory disease. N. Engl. J. Med. 383, 2628–2638 (2020). This paper reports a newly defined inflammatory syndrome that overlaps phenotypically with MDS.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Giannouli, S., Kanellopoulou, T. & Voulgarelis, M. Myelodysplasia and autoimmunity. Curr. Opin. Rheumatol. 24, 97–102 (2012).

    Article  CAS  PubMed  Google Scholar 

  61. Huang, H. et al. VEXAS syndrome in myelodysplastic syndrome with autoimmune disorder. Exp. Hematol. Oncol. 10, 23 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Klco, J. M. & Mullighan, C. G. Advances in germline predisposition to acute leukaemias and myeloid neoplasms. Nat. Rev. Cancer 21, 122–137 (2021).

    Article  CAS  PubMed  Google Scholar 

  63. Kennedy, A. L. & Shimamura, A. Genetic predisposition to MDS: clinical features and clonal evolution. Blood 133, 1071–1085 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Baliakas, P. et al. Nordic guidelines for germline predisposition to myeloid neoplasms in adults: recommendations for genetic diagnosis, clinical management and follow-up. Hemasphere 3, e321 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  65. Sebert, M. et al. Germline DDX41 mutations define a significant entity within adult MDS/AML patients. Blood 134, 1441–1444 (2019).

    Article  PubMed  Google Scholar 

  66. Nagata, Y. et al. Germline loss-of-function SAMD9 and SAMD9L alterations in adult myelodysplastic syndromes. Blood 132, 2309–2313 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Wlodarski, M. W. et al. Prevalence, clinical characteristics, and prognosis of GATA2-related myelodysplastic syndromes in children and adolescents. Blood 127, 1387–1397 (2016).

    Article  CAS  PubMed  Google Scholar 

  68. Gale, R. P. & Bennett, J. M. Are myelodysplastic syndromes and acute myeloid leukemia one disease? Leuk. Res. 33, 351–354 (2009).

    Article  PubMed  Google Scholar 

  69. Glenthoj, A. et al. Immune mechanisms in myelodysplastic syndrome. Int. J. Mol. Sci. https://doi.org/10.3390/ijms17060944 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  70. Barreyro, L., Chlon, T. M. & Starczynowski, D. T. Chronic immune response dysregulation in MDS pathogenesis. Blood 132, 1553–1560 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Ratajczak, M. Z. et al. The Nlrp3 inflammasome as a “rising star” in studies of normal and malignant hematopoiesis. Leukemia 34, 1512–1523 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  72. Scheinberg, P., Marte, M., Nunez, O. & Young, N. S. Paroxysmal nocturnal hemoglobinuria clones in severe aplastic anemia patients treated with horse anti-thymocyte globulin plus cyclosporine. Haematologica 95, 1075–1080 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Wang, S. A. et al. Detection of paroxysmal nocturnal hemoglobinuria clones in patients with myelodysplastic syndromes and related bone marrow diseases, with emphasis on diagnostic pitfalls and caveats. Haematologica 94, 29–37 (2009).

    Article  PubMed  Google Scholar 

  74. Schratz, K. E. & DeZern, A. E. Genetic predisposition to myelodysplastic syndrome in clinical practice. Hematol. Oncol. Clin. North Am. 34, 333–356 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  75. Keung, Y. K. et al. Bone marrow cytogenetic abnormalities of aplastic anemia. Am. J. Hematol. 66, 167–171 (2001).

    Article  CAS  PubMed  Google Scholar 

  76. Araten, D. J. et al. Cytogenetic and morphological abnormalities in paroxysmal nocturnal haemoglobinuria. Br. J. Haematol. 115, 360–368 (2001).

    Article  CAS  PubMed  Google Scholar 

  77. Raza, A. & Galili, N. The genetic basis of phenotypic heterogeneity in myelodysplastic syndromes. Nat. Rev. Cancer 12, 849–859 (2012).

    Article  CAS  PubMed  Google Scholar 

  78. Haferlach, T. et al. Landscape of genetic lesions in 944 patients with myelodysplastic syndromes. Leukemia 28, 241–247 (2014). A paper reporting the mutation topography of MDS.

    Article  CAS  PubMed  Google Scholar 

  79. Yoshizato, T. et al. Somatic mutations and clonal hematopoiesis in aplastic anemia. N. Engl. J. Med. 373, 35–47 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Li, L. et al. Gene mutations associated with thrombosis detected by whole-exome sequencing in paroxysmal nocturnal hemoglobinuria. Int. J. Lab. Hematol. 41, 424–432 (2019).

    Article  PubMed  Google Scholar 

  81. Dohner, H. et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood 129, 424–447 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  82. Herold, T. et al. Validation and refinement of the revised 2017 European LeukemiaNet genetic risk stratification of acute myeloid leukemia. Leukemia 34, 3161–3172 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Kasahara, K. et al. Cytogenetically unrelated clones in acute myeloid leukemia showing different responses to chemotherapy. Case Rep. Hematol. 2016, 2373902 (2016).

    PubMed  PubMed Central  Google Scholar 

  84. Cooper, J. N. & Young, N. S. Clonality in context: hematopoietic clones in their marrow environment. Blood 130, 2363–2372 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Arber, D. A. et al. International consensus classification of myeloid neoplasms and acute leukemia: integrating morphological, clinical, and genomic data. Blood https://doi.org/10.1182/blood.2022015850 (2022). This publication is the ICC of MDS.

    Article  PubMed  Google Scholar 

  86. Balaian, E., Wobus, M., Bornhauser, M., Chavakis, T. & Sockel, K. Myelodysplastic syndromes and metabolism. Int. J. Mol. Sci. https://doi.org/10.3390/ijms222011250 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  87. Ganan-Gomez, I. et al. Deregulation of innate immune and inflammatory signaling in myelodysplastic syndromes. Leukemia 29, 1458–1469 (2015). This review provides an overview of the altered immunity in MDS.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Trowbridge, J. J. & Starczynowski, D. T. Innate immune pathways and inflammation in hematopoietic aging, clonal hematopoiesis, and MDS. J. Exp. Med. 218, e20201544 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Yoshida, K. et al. Frequent pathway mutations of splicing machinery in myelodysplasia. Nature 478, 64–69 (2011).

    Article  CAS  PubMed  Google Scholar 

  90. Cazzola, M., Della Porta, M. G. & Malcovati, L. The genetic basis of myelodysplasia and its clinical relevance. Blood 122, 4021–4034 (2013). This review discusses the genetic alterations in MDS and their clinical relevance.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Huang, H. et al. Is race important in genomic classification of hematological neoplasms? Hematol. Oncol. https://doi.org/10.1002/hon.2909 (2021).

    Article  PubMed  Google Scholar 

  92. Nagata, Y. et al. Machine learning demonstrates that somatic mutations imprint invariant morphologic features in myelodysplastic syndromes. Blood 136, 2249–2262 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  93. Ebert, B. L. et al. Identification of RPS14 as a 5q- syndrome gene by RNA interference screen. Nature 451, 335–339 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Krönke, J. et al. Lenalidomide induces ubiquitination and degradation of CK1α in del(5q) MDS. Nature 523, 183–188 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  95. Haase, D. et al. TP53 mutation status divides myelodysplastic syndromes with complex karyotypes into distinct prognostic subgroups. Leukemia 33, 1747–1758 (2019). This paper reports the role of TP53 mutation and cytogenetics in MDS.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Bernard, E. et al. Implications of TP53 allelic state for genome stability, clinical presentation and outcomes in myelodysplastic syndromes. Nat. Med. 26, 1549–1556 (2020). This paper reports the implications of TP53 allelic state in MDS.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Jann, J. C. & Tothova, Z. Cohesin mutations in myeloid malignancies. Blood 138, 649–661 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Kon, A. et al. Recurrent mutations in multiple components of the cohesin complex in myeloid neoplasms. Nat. Genet. 45, 1232–1237 (2013).

    Article  CAS  PubMed  Google Scholar 

  99. Ogawa, S. Genetics of MDS. Blood 133, 1049–1059 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Sperling, A. S., Gibson, C. J. & Ebert, B. L. The genetics of myelodysplastic syndrome: from clonal haematopoiesis to secondary leukaemia. Nat. Rev. Cancer 17, 5–19 (2017).

    Article  CAS  PubMed  Google Scholar 

  101. Bejar, R. CHIP, ICUS, CCUS and other four-letter words. Leukemia 31, 1869–1871 (2017). This review article discusses clonal haematopoiesis and MDS predisposition.

    Article  CAS  PubMed  Google Scholar 

  102. Malcovati, L. et al. Clinical significance of somatic mutation in unexplained blood cytopenia. Blood 129, 3371–3378 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. DeZern, A. E., Malcovati, L. & Ebert, B. L. CHIP, CCUS, and other acronyms: definition, implications, and impact on practice. Am. Soc. Clin. Oncol. Educ. Book 39, 400–410 (2019).

    Article  PubMed  Google Scholar 

  104. Wong, T. N. et al. Role of TP53 mutations in the origin and evolution of therapy-related acute myeloid leukaemia. Nature 518, 552–555 (2015).

    Article  CAS  PubMed  Google Scholar 

  105. Bick, A. G. et al. Inherited causes of clonal haematopoiesis in 97,691 whole genomes. Nature 586, 763–768 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Figueroa, M. E. et al. MDS and secondary AML display unique patterns and abundance of aberrant DNA methylation. Blood 114, 3448–3458 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Jiang, Y. et al. Aberrant DNA methylation is a dominant mechanism in MDS progression to AML. Blood 113, 1315–1325 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Nagata, Y. & Maciejewski, J. P. The functional mechanisms of mutations in myelodysplastic syndrome. Leukemia 33, 2779–2794 (2019). The review discusses the role of mutations in MDS.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Stein, E. M. et al. Enasidenib in patients with mutant IDH2 myelodysplastic syndromes: a phase 1 subgroup analysis of the multicentre, AG221-C-001 trial. Lancet Haematol. 7, e309–e319 (2020).

    Article  PubMed  Google Scholar 

  110. Montesinos, P. et al. Ivosidenib and azacitidine in IDH1-mutated acute myeloid leukemia. N. Engl. J. Med. 386, 1519–1531 (2022).

    Article  CAS  PubMed  Google Scholar 

  111. Kim, E. et al. SRSF2 mutations contribute to myelodysplasia by mutant-specific effects on exon recognition. Cancer Cell 27, 617–630 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Liang, Y. et al. SRSF2 mutations drive oncogenesis by activating a global program of aberrant alternative splicing in hematopoietic cells. Leukemia 32, 2659–2671 (2018). This paper reports the functional effects of SRSF2 mutations in MDS.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Santini, V. et al. Impact of somatic mutations on response to lenalidomide in lower-risk non-del(5q) myelodysplastic syndromes patients. Leukemia 35, 897–900 (2021).

    Article  PubMed  Google Scholar 

  114. Singh, S. et al. SF3B1 mutations induce R-loop accumulation and DNA damage in MDS and leukemia cells with therapeutic implications. Leukemia 34, 2525–2530 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  115. Larrayoz, M. et al. The SF3B1 inhibitor spliceostatin A (SSA) elicits apoptosis in chronic lymphocytic leukaemia cells through downregulation of Mcl-1. Leukemia 30, 351–360 (2016).

    Article  CAS  PubMed  Google Scholar 

  116. Bonnal, S. C., Lopez-Oreja, I. & Valcarcel, J. Roles and mechanisms of alternative splicing in cancer — implications for care. Nat. Rev. Clin. Oncol. 17, 457–474 (2020).

    Article  PubMed  Google Scholar 

  117. Malcovati, L. et al. SF3B1-mutant MDS as a distinct disease subtype: a proposal from the International Working Group for the Prognosis of MDS. Blood 136, 157–170 (2020). This study proposes a new disease subtype: SF3B1-mutant MDS.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Graubert, T. A. et al. Recurrent mutations in the U2AF1 splicing factor in myelodysplastic syndromes. Nat. Genet. 44, 53–57 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  119. Li, B. et al. Clinical features and biological implications of different U2AF1 mutation types in myelodysplastic syndromes. Genes Chromosomes Cancer 57, 80–88 (2018).

    Article  CAS  PubMed  Google Scholar 

  120. Ilagan, J. O. et al. U2AF1 mutations alter splice site recognition in hematological malignancies. Genome Res. 25, 14–26 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Park, S. M. et al. U2AF35(S34F) promotes transformation by directing aberrant ATG7 Pre-mRNA 3’ end formation. Mol. Cell 62, 479–490 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Smith, M. A. et al. U2AF1 mutations induce oncogenic IRAK4 isoforms and activate innate immune pathways in myeloid malignancies. Nat. Cell Biol. 21, 640–650 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Choudhary, G. S. et al. Activation of targetable inflammatory immune signaling is seen in myelodysplastic syndromes with SF3B1 mutations. eLife https://doi.org/10.7554/eLife.78136 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  124. Damm, F. et al. Mutations affecting mRNA splicing define distinct clinical phenotypes and correlate with patient outcome in myelodysplastic syndromes. Blood 119, 3211–3218 (2012).

    Article  CAS  PubMed  Google Scholar 

  125. Madan, V. et al. Aberrant splicing of U12-type introns is the hallmark of ZRSR2 mutant myelodysplastic syndrome. Nat. Commun. 6, 6042 (2015).

    Article  CAS  PubMed  Google Scholar 

  126. Taylor, J. et al. Single-cell genomics reveals the genetic and molecular bases for escape from mutational epistasis in myeloid neoplasms. Blood 136, 1477–1486 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  127. Yoshimi, A. et al. Coordinated alterations in RNA splicing and epigenetic regulation drive leukaemogenesis. Nature 574, 273–277 (2019). This paper reports on the crosstalk between mutations in MDS.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Michiels, J. J., van der Meulen, J. & Brederoo, P. The natural history of trilinear myelodysplastic syndrome and erythroleukemia. Haematologica 82, 452–454 (1997).

    CAS  PubMed  Google Scholar 

  129. Bennett, J. M. & Komrokji, R. S. The myelodysplastic syndromes: diagnosis, molecular biology and risk assessment. Hematology 10 (Suppl. 1), 258–269 (2005).

    Article  CAS  PubMed  Google Scholar 

  130. Layton, D. M. & Mufti, G. J. Myelodysplastic syndromes: their history, evolution and relation to acute myeloid leukaemia. Blut 53, 423–436 (1986).

    Article  CAS  PubMed  Google Scholar 

  131. Bennett, J. M. et al. Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group. Br. J. Haematol. 33, 451–458 (1976).

    Article  CAS  PubMed  Google Scholar 

  132. Bennett, J. M. et al. Proposals for the classification of the myelodysplastic syndromes. Br. J. Haematol. 51, 189–199 (1982).

    Article  CAS  PubMed  Google Scholar 

  133. Harris, N. L. et al. World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997. J. Clin. Oncol. 17, 3835–3849 (1999).

    Article  CAS  PubMed  Google Scholar 

  134. Vardiman, J. W., Harris, N. L. & Brunning, R. D. The World Health Organization (WHO) classification of the myeloid neoplasms. Blood 100, 2292–2302 (2002).

    Article  CAS  PubMed  Google Scholar 

  135. Vardiman, J. W. et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 114, 937–951 (2009).

    Article  CAS  PubMed  Google Scholar 

  136. Arber, D. A. et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 127, 2391–2405 (2016).

    Article  CAS  PubMed  Google Scholar 

  137. Niemeyer, C. M. & Baumann, I. Classification of childhood aplastic anemia and myelodysplastic syndrome. Hematol. Am. Soc. Hematol. Educ. Program 2011, 84–89 (2011).

    Article  Google Scholar 

  138. Invernizzi, R., Quaglia, F. & Porta, M. G. Importance of classical morphology in the diagnosis of myelodysplastic syndrome. Mediterr. J. Hematol. Infect. Dis. 7, e2015035 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  139. Feng, G. et al. A systematic classification of megakaryocytic dysplasia and its impact on prognosis for patients with myelodysplastic syndromes. Exp. Hematol. Oncol. 5, 12 (2015).

    Article  PubMed  Google Scholar 

  140. Kussick, S. J. et al. Four-color flow cytometry shows strong concordance with bone marrow morphology and cytogenetics in the evaluation for myelodysplasia. Am. J. Clin. Pathol. 124, 170–181 (2005).

    Article  PubMed  Google Scholar 

  141. Bento, L. C. et al. The use of flow cytometry in myelodysplastic syndromes: a review. Front. Oncol. 7, 270 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  142. Greenberg, P. L. et al. Revised international prognostic scoring system for myelodysplastic syndromes. Blood 120, 2454–2465 (2012). This paper presents the IPSS-R for MDS.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Schanz, J. et al. New comprehensive cytogenetic scoring system for primary myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia after MDS derived from an international database merge. J. Clin. Oncol. 30, 820–829 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  144. Jadersten, M. et al. TP53 mutations in low-risk myelodysplastic syndromes with del(5q) predict disease progression. J. Clin. Oncol. 29, 1971–1979 (2011).

    Article  PubMed  Google Scholar 

  145. Soenen, V. et al. 17p Deletion in acute myeloid leukemia and myelodysplastic syndrome. Analysis of breakpoints and deleted segments by fluorescence in situ. Blood 91, 1008–1015 (1998).

    Article  CAS  PubMed  Google Scholar 

  146. Yoshizato, T. et al. Genetic abnormalities in myelodysplasia and secondary acute myeloid leukemia: impact on outcome of stem cell transplantation. Blood 129, 2347–2358 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Haase, D. Cytogenetic features in myelodysplastic syndromes. Ann. Hematol. 87, 515–526 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  148. Haase, D. et al. New insights into the prognostic impact of the karyotype in MDS and correlation with subtypes: evidence from a core dataset of 2124 patients. Blood 110, 4385–4395 (2007).

    Article  CAS  PubMed  Google Scholar 

  149. Jacoby, M. A. & Walter, M. J. Detection of copy number alterations in acute myeloid leukemia and myelodysplastic syndromes. Expert Rev. Mol. Diagn. 12, 253–264 (2012).

    Article  CAS  PubMed  Google Scholar 

  150. Greenberg, P. et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 89, 2079–2088 (1997).

    Article  CAS  PubMed  Google Scholar 

  151. Nazha, A. et al. Personalized prediction model to risk stratify patients with myelodysplastic syndromes. J. Clin. Oncol. 39, 3737–3746 (2021).

    Article  CAS  PubMed  Google Scholar 

  152. Bernard, E. et al. Molecular international prognostic scoring system for myelodysplastic syndromes. NEJM Evid. 1, 10.1056/EVIDoa2200008 (2022). This paper presents the IPSS-M for MDS.

  153. Malcovati, L. et al. Time-dependent prognostic scoring system for predicting survival and leukemic evolution in myelodysplastic syndromes. J. Clin. Oncol. 25, 3503–3510 (2007).

    Article  PubMed  Google Scholar 

  154. Malcovati, L. et al. Prognostic factors and life expectancy in myelodysplastic syndromes classified according to WHO criteria: a basis for clinical decision making. J. Clin. Oncol. 23, 7594–7603 (2005).

    Article  PubMed  Google Scholar 

  155. Santini, V. et al. Can the revised IPSS predict response to erythropoietic-stimulating agents in patients with classical IPSS low or intermediate-1 MDS? Blood 122, 2286–2288 (2013).

    Article  CAS  PubMed  Google Scholar 

  156. Sekeres, M. A. et al. Validation of the IPSS-R in lenalidomide-treated, lower-risk myelodysplastic syndrome patients with del(5q). Blood Cancer J. 4, e242 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Park, M. J. et al. Is International Prognostic Scoring System (IPSS) still standard in predicting prognosis in patients with myelodysplastic syndrome? External validation of the WHO Classification-Based Prognostic Scoring System (WPSS) and comparison with IPSS. Eur. J. Haematol. 81, 364–373 (2008).

    PubMed  Google Scholar 

  158. Della Porta, M. G. et al. Validation of WHO classification-based Prognostic Scoring System (WPSS) for myelodysplastic syndromes and comparison with the revised International Prognostic Scoring System (IPSS-R). A study of the International Working Group for Prognosis in Myelodysplasia (IWG-PM). Leukemia 29, 1502–1513 (2015).

    Article  PubMed  Google Scholar 

  159. Nazha, A. et al. Incorporation of molecular data into the Revised International Prognostic Scoring System in treated patients with myelodysplastic syndromes. Leukemia 30, 2214–2220 (2016).

    Article  CAS  PubMed  Google Scholar 

  160. Nazha, A. et al. Adding molecular data to prognostic models can improve predictive power in treated patients with myelodysplastic syndromes. Leukemia 31, 2848–2850 (2017). This study reports the application of mutation data to prognostic models.

    Article  CAS  PubMed  Google Scholar 

  161. Nazha, A. et al. Personalized prediction model to risk stratify patients with Myelodysplastic syndromes. J. Clin. Oncol. https://doi.org/10.1200/JCO.20.02810 (2021).

    Article  PubMed  Google Scholar 

  162. Cutler, C. S. et al. A decision analysis of allogeneic bone marrow transplantation for the myelodysplastic syndromes: delayed transplantation for low-risk myelodysplasia is associated with improved outcome. Blood 104, 579–585 (2004).

    Article  CAS  PubMed  Google Scholar 

  163. Gale, R. P., Bennett, J. M. & Hoffman, F. O. Therapy-related AML: a slip of the lip can sink a ship. Leuk. Res. 38, 418–420 (2014).

    Article  PubMed  Google Scholar 

  164. Gale, R. P., Bennett, J. M. & Hoffman, F. O. Who has therapy-related AML? Mediterr. J. Hematol. Infect. Dis. 9, e2017025 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  165. Yang, H. et al. High-resolution structural variant profiling of myelodysplastic syndromes by optical genome mapping uncovers cryptic aberrations of prognostic and therapeutic significance. Leukemia 36, 2306–2316 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Wang, Z. Y. & Chen, Z. Acute promyelocytic leukemia: from highly fatal to highly curable. Blood 111, 2505–2515 (2008).

    Article  CAS  PubMed  Google Scholar 

  167. de Thé, H., Pandolfi, P. P. & Chen, Z. Acute promyelocytic leukemia: a paradigm for oncoprotein-targeted cure. Cancer Cell 32, 552–560 (2017).

    Article  PubMed  Google Scholar 

  168. de Thé, H. & Chen, Z. Acute promyelocytic leukaemia: novel insights into the mechanisms of cure. Nat. Rev. Cancer 10, 775–783 (2010).

    Article  PubMed  Google Scholar 

  169. Fenaux, P. & Ades, L. How we treat lower-risk myelodysplastic syndromes. Blood 121, 4280–4286 (2013).

    Article  CAS  PubMed  Google Scholar 

  170. Sekeres, M. A. & Cutler, C. How we treat higher-risk myelodysplastic syndromes. Blood 123, 829–836 (2014).

    Article  CAS  PubMed  Google Scholar 

  171. Daver, N. et al. Hypomethylating agents in combination with immune checkpoint inhibitors in acute myeloid leukemia and myelodysplastic syndromes. Leukemia 32, 1094–1105 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Greenberg, P. L. et al. Myelodysplastic syndromes, version 2.2017, NCCN clinical practice guidelines in oncology. J. Natl Compr. Canc Netw. 15, 60–87 (2017).

    Article  PubMed  Google Scholar 

  173. Bejar, R. Advances in personalized therapeutic approaches in myelodysplastic syndromes. J. Natl Compr. Canc Netw. 17, 1444–1447 (2019).

    Article  PubMed  Google Scholar 

  174. Fenaux, P. et al. Myelodysplastic syndromes: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 32, 142–156 (2021).

    Article  CAS  PubMed  Google Scholar 

  175. Platzbecker, U. Treatment of MDS. Blood 133, 1096–1107 (2019). This review article discusses therapeutic strategies in MDS.

    Article  CAS  PubMed  Google Scholar 

  176. Garelius, H. K. et al. Erythropoiesis-stimulating agents significantly delay the onset of a regular transfusion need in nontransfused patients with lower-risk myelodysplastic syndrome. J. Intern. Med. 281, 284–299 (2017).

    Article  CAS  PubMed  Google Scholar 

  177. Golshayan, A. R. et al. Efficacy of growth factors compared to other therapies for low-risk myelodysplastic syndromes. Br. J. Haematol. 137, 125–132 (2007).

    Article  CAS  PubMed  Google Scholar 

  178. Platzbecker, U. et al. A phase 3 randomized placebo-controlled trial of darbepoetin alfa in patients with anemia and lower-risk myelodysplastic syndromes. Leukemia 31, 1944–1950 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Malcovati, L. et al. SF3B1 mutation identifies a distinct subset of myelodysplastic syndrome with ring sideroblasts. Blood 126, 233–241 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  180. Suragani, R. N. V. S. et al. Transforming growth factor-β superfamily ligand trap ACE-536 corrects anemia by promoting late-stage erythropoiesis. Nat. Med. 20, 408–414 (2014).

    Article  CAS  PubMed  Google Scholar 

  181. Fenaux, P. et al. Luspatercept in patients with lower-risk Myelodysplastic Syndromes. N. Engl. J. Med. 382, 140–151 (2020). This paper reports a clinical trial of luspatercept in lower-risk MDS.

    Article  CAS  PubMed  Google Scholar 

  182. Fenaux, P. et al. A randomized phase 3 study of lenalidomide versus placebo in RBC transfusion-dependent patients with Low-/Intermediate-1-risk myelodysplastic syndromes with del5q. Blood 118, 3765–3776 (2011).

    Article  CAS  PubMed  Google Scholar 

  183. Bussel, J. B. et al. A review of romiplostim mechanism of action and clinical applicability. Drug Des. Devel Ther. 15, 2243–2268 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  184. Oliva, E. N. et al. Eltrombopag versus placebo for low-risk myelodysplastic syndromes with thrombocytopenia (EQoL-MDS): phase 1 results of a single-blind, randomised, controlled, phase 2 superiority trial. Lancet Haematol. 4, e127–e136 (2017).

    Article  PubMed  Google Scholar 

  185. Giagounidis, A. et al. Results of a randomized, double-blind study of romiplostim versus placebo in patients with low/intermediate-1-risk myelodysplastic syndrome and thrombocytopenia. Cancer 120, 1838–1846 (2014).

    Article  CAS  PubMed  Google Scholar 

  186. Saunthararajah, Y. et al. p53-Independent, Normal stem cell sparing epigenetic differentiation therapy for myeloid and other malignancies. Semin. Oncol. 39, 97–108 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. Cheson, B. D. et al. Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia. Blood 108, 419–425 (2006).

    Article  CAS  PubMed  Google Scholar 

  188. Komrokji, R. et al. Azacitidine in lower-risk myelodysplastic syndromes: a meta-analysis of data from prospective studies. Oncologist 23, 159–170 (2018).

    Article  PubMed  Google Scholar 

  189. Garcia-Manero, G. et al. Oral cedazuridine/decitabine for MDS and CMML: a phase 2 pharmacokinetic/pharmacodynamic randomized crossover study. Blood 136, 674–683 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  190. Komrokji, R. S. et al. A phase II multicenter rabbit anti-thymocyte globulin trial in patients with myelodysplastic syndromes identifying a novel model for response prediction. Haematologica 99, 1176–1183 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  191. Passweg, J. R. et al. Immunosuppressive therapy for patients with Myelodysplastic syndrome: a prospective randomized multicenter phase III trial comparing antithymocyte globulin plus cyclosporine with best supportive care — SAKK 33/99. J. Clin. Oncol. 29, 303–309 (2011).

    Article  CAS  PubMed  Google Scholar 

  192. Angelucci, E. et al. Iron chelation in transfusion-dependent patients with low- to intermediate-1-risk Myelodysplastic syndromes: a randomized trial. Ann. Intern. Med. 172, 513–522 (2020). This paper reports a clinical trial on iron chelation in MDS.

    Article  PubMed  Google Scholar 

  193. Papaemmanuil, E. et al. Clinical and biological implications of driver mutations in myelodysplastic syndromes. Blood 122, 3616–3627 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  194. Papageorgiou, S. G. et al. Serum ferritin and ECOG performance status predict the response and improve the prognostic value of IPSS or IPSS-R in patients with high-risk myelodysplastic syndromes and oligoblastic acute myeloid leukemia treated with 5-azacytidine: a retrospective analysis of the Hellenic national registry of myelodysplastic and hypoplastic syndromes. Ther. Adv. Hematol. 11, 2040620720966121 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  195. Rasmussen, B. et al. Randomized phase II study of azacitidine +/− lenalidomide in higher-risk myelodysplastic syndromes and acute myeloid leukemia with a karyotype including Del(5q). Leukemia 36, 1436–1439 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  196. Greenberg, P. L. et al. NCCN Guidelines(R) Insights: myelodysplastic syndromes, version 3.2022. J. Natl Compr. Canc Netw. 20, 106–117 (2022).

    Article  PubMed  Google Scholar 

  197. Fenaux, P. et al. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. 10, 223–232 (2009). This paper reports a phase III study of azacitidine in the treatment of higher-risk MDS.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  198. Platzbecker, U. et al. Measurable residual disease-guided treatment with azacitidine to prevent haematological relapse in patients with myelodysplastic syndrome and acute myeloid leukaemia (RELAZA2): an open-label, multicentre, phase 2 trial. Lancet Oncol. 19, 1668–1679 (2018).

    Article  CAS  PubMed  Google Scholar 

  199. Diez-Campelo, M. et al. Azacitidine improves outcome in higher-risk MDS patients with chromosome 7 abnormalities: a retrospective comparison of GESMD and GFM registries. Br. J. Haematol. 181, 350–359 (2018).

    Article  CAS  PubMed  Google Scholar 

  200. Bernal, T. et al. Effectiveness of azacitidine in unselected high-risk myelodysplastic syndromes: results from the Spanish registry. Leukemia 29, 1875–1881 (2015).

    Article  CAS  PubMed  Google Scholar 

  201. Mozessohn, L. et al. Azacitidine in the ‘real-world’: an evaluation of 1101 higher-risk myelodysplastic syndrome/low blast count acute myeloid leukaemia patients in Ontario, Canada. Br. J. Haematol. 181, 803–815 (2018).

    Article  CAS  PubMed  Google Scholar 

  202. Zeidan, A. M. et al. A call for action: increasing enrollment of untreated patients with higher-risk myelodysplastic syndromes in first-line clinical trials. Cancer 123, 3662–3672 (2017).

    Article  PubMed  Google Scholar 

  203. Lubbert, M. et al. Low-dose decitabine versus best supportive care in elderly patients with intermediate- or high-risk myelodysplastic syndrome (MDS) ineligible for intensive chemotherapy: final results of the randomized phase III study of the European Organisation for Research and Treatment of Cancer Leukemia Group and the German MDS Study Group. J. Clin. Oncol. 29, 1987–1996 (2011).

    Article  PubMed  Google Scholar 

  204. Kantarjian, H. et al. Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study. Cancer 106, 1794–1803 (2006).

    Article  CAS  PubMed  Google Scholar 

  205. Jasielec, J., Saloura, V. & Godley, L. A. The mechanistic role of DNA methylation in myeloid leukemogenesis. Leukemia 28, 1765–1773 (2014).

    Article  CAS  PubMed  Google Scholar 

  206. Issa, J. P. Decitabine. Curr. Opin. Oncol. 15, 446–451 (2003).

    Article  CAS  PubMed  Google Scholar 

  207. Duncavage, E. J. et al. Mutation clearance after transplantation for myelodysplastic syndrome. N. Engl. J. Med. 379, 1028–1041 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  208. Chang, C. K. et al. TP53 mutations predict decitabine-induced complete responses in patients with myelodysplastic syndromes. Br. J. Haematol. 176, 600–608 (2017).

    Article  CAS  PubMed  Google Scholar 

  209. Nazha, A. et al. A personalized prediction model for outcomes after allogeneic hematopoietic cell transplant in patients with myelodysplastic syndromes. Biol. Blood Marrow Transpl. 26, 2139–2146 (2020).

    Article  CAS  Google Scholar 

  210. Gale, R. P. & Pusic, I. Transplants for MDS and quality-of-life. But whose quality-of-life? Bone Marrow Transpl. 51, 1066–1068 (2016).

    Article  CAS  Google Scholar 

  211. Shaffer, B. C. et al. Scoring system prognostic of outcome in patients undergoing allogeneic hematopoietic cell transplantation for Myelodysplastic syndrome. J. Clin. Oncol. 34, 1864–1871 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  212. Anderson, J. E. et al. Allogeneic bone marrow transplantation for 93 patients with myelodysplastic syndrome. Blood 82, 677–681 (1993).

    Article  CAS  PubMed  Google Scholar 

  213. Barker, J. N. et al. Transplantation of 2 partially HLA-matched umbilical cord blood units to enhance engraftment in adults with hematologic malignancy. Blood 105, 1343–1347 (2005).

    Article  CAS  PubMed  Google Scholar 

  214. De Witte, T. et al. Allogeneic bone marrow transplantation for secondary leukaemia and myelodysplastic syndrome: a survey by the Leukaemia Working Party of the European Bone Marrow Transplantation Group (EBMTG). Br. J. Haematol. 74, 151–155 (1990).

    Article  PubMed  Google Scholar 

  215. Demuynck, H. et al. Treatment of patients with myelodysplastic syndromes with allogeneic bone marrow transplantation from genotypically HLA-identical sibling and alternative donors. Bone Marrow Transpl. 17, 745–751 (1996).

    CAS  Google Scholar 

  216. Jurado, M. et al. Hematopoietic stem cell transplantation for advanced myelodysplastic syndrome after conditioning with busulfan and fractionated total body irradiation is associated with low relapse rate but considerable nonrelapse mortality. Biol. Blood Marrow Transpl. 8, 161–169 (2002).

    Article  Google Scholar 

  217. Kerbauy, D. M. et al. Allogeneic hematopoietic cell transplantation for chronic myelomonocytic leukemia. Biol. Blood Marrow Transpl. 11, 713–720 (2005).

    Article  Google Scholar 

  218. Laughlin, M. J. et al. Outcomes after transplantation of cord blood or bone marrow from unrelated donors in adults with leukemia. N. Engl. J. Med. 351, 2265–2275 (2004).

    Article  CAS  PubMed  Google Scholar 

  219. Luznik, L. et al. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol. Blood Marrow Transpl. 14, 641–650 (2008).

    Article  CAS  Google Scholar 

  220. Nevill, T. J. et al. Cytogenetic abnormalities in primary myelodysplastic syndrome are highly predictive of outcome after allogeneic bone marrow transplantation. Blood 92, 1910–1917 (1998).

    Article  CAS  PubMed  Google Scholar 

  221. Scott, B. L. et al. Myeloablative vs nonmyeloablative allogeneic transplantation for patients with myelodysplastic syndrome or acute myelogenous leukemia with multilineage dysplasia: a retrospective analysis. Leukemia 20, 128–135 (2006).

    Article  CAS  PubMed  Google Scholar 

  222. Wallen, H. et al. Ablative allogeneic hematopoietic cell transplantation in adults 60 years of age and older. J. Clin. Oncol. 23, 3439–3446 (2005).

    Article  PubMed  Google Scholar 

  223. Alessandrino, E. P. et al. Optimal timing of allogeneic hematopoietic stem cell transplantation in patients with myelodysplastic syndrome. Am. J. Hematol. 88, 581–588 (2013). This paper reports a clinical trial investigating the optimal timing of transplantation in MDS.

    Article  PubMed  PubMed Central  Google Scholar 

  224. Getta, B. M. et al. Allogeneic hematopoietic stem cell transplantation is underutilized in older patients with Myelodysplastic syndromes. Biol. Blood Marrow Transpl. 23, 1078–1086 (2017).

    Article  Google Scholar 

  225. Lindsley, R. C. et al. Prognostic mutations in myelodysplastic syndrome after stem-cell transplantation. N. Engl. J. Med. 376, 536–547 (2017). This study reports on the impact of mutations on transplantation outcomes.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  226. Grunwald, M. R. et al. Alternative donor transplantation for myelodysplastic syndromes: haploidentical relative and matched unrelated donors. Blood Adv. 5, 975–983 (2021).

    Article  CAS  PubMed  Google Scholar 

  227. Nakamura, R. et al. Biologic assignment trial of reduced-intensity hematopoietic cell transplantation based on donor availability in patients 50–75 years of age with advanced myelodysplastic syndrome. J. Clin. Oncol. https://doi.org/10.1200/JCO.20.03380 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  228. Abel, G. A. et al. Fit older adults with advanced myelodysplastic syndromes: who is most likely to benefit from transplant? Leukemia 35, 1166–1175 (2021).

    Article  CAS  PubMed  Google Scholar 

  229. Gerds, A. T. et al. Outcomes after umbilical cord blood transplantation for myelodysplastic syndromes. Biol. Blood Marrow Transpl. 23, 971–979 (2017).

    Article  Google Scholar 

  230. de Witte, T. et al. Allogeneic hematopoietic stem cell transplantation for MDS and CMML: recommendations from an international expert panel. Blood 129, 1753–1762 (2017). This paper provides transplantation recommendations in MDS and CMML.

    Article  PubMed  PubMed Central  Google Scholar 

  231. Robin, M. et al. Comparison of unrelated cord blood and peripheral blood stem cell transplantation in adults with myelodysplastic syndrome after reduced-intensity conditioning regimen: a collaborative study from Eurocord (Cord blood Committee of Cellular Therapy & Immunobiology Working Party of EBMT) and Chronic Malignancies Working Party. Biol. Blood Marrow Transpl. 21, 489–495 (2015).

    Article  Google Scholar 

  232. Gerds, A. T. et al. Pretransplantation therapy with azacitidine vs induction chemotherapy and posttransplantation outcome in patients with MDS. Biol. Blood Marrow Transpl. 18, 1211–1218 (2012).

    Article  CAS  Google Scholar 

  233. Kroger, N. et al. Comparison between 5-azacytidine treatment and allogeneic stem-cell transplantation in elderly patients with advanced MDS according to donor availability (VidazaAllo Study). J. Clin. Oncol. 39, 3318–3327 (2021).

    Article  PubMed  Google Scholar 

  234. Oliansky, D. M. et al. The role of cytotoxic therapy with hematopoietic stem cell transplantation in the therapy of myelodysplastic syndromes: an evidence-based review. Biol. Blood Marrow Transpl. 15, 137–172 (2009).

    Article  Google Scholar 

  235. Fenaux, P. et al. Myelodysplastic syndromes: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 25 (Suppl. 3), iii57–iii69 (2014).

    Article  PubMed  Google Scholar 

  236. Atallah, E. et al. Comparison of patient age groups in transplantation for Myelodysplastic syndrome: the medicare coverage with evidence development study. JAMA Oncol. 6, 486–493 (2020).

    Article  PubMed  Google Scholar 

  237. Laport, G. G. et al. Reduced-intensity conditioning followed by allogeneic hematopoietic cell transplantation for adult patients with myelodysplastic syndrome and myeloproliferative disorders. Biol. Blood Marrow Transpl. 14, 246–255 (2008).

    Article  Google Scholar 

  238. Deeg, H. J. et al. Conditioning with targeted busulfan and cyclophosphamide for hemopoietic stem cell transplantation from related and unrelated donors in patients with myelodysplastic syndrome. Blood 100, 1201–1207 (2002).

    Article  CAS  PubMed  Google Scholar 

  239. Runde, V. et al. Bone marrow transplantation from HLA-identical siblings as first-line treatment in patients with myelodysplastic syndromes: early transplantation is associated with improved outcome. Chronic Leukemia Working Party of the European Group for blood and marrow transplantation. Bone Marrow Transpl. 21, 255–261 (1998).

    Article  CAS  Google Scholar 

  240. Beelen, D. W. et al. Treosulfan or busulfan plus fludarabine as conditioning treatment before allogeneic haemopoietic stem cell transplantation for older patients with acute myeloid leukaemia or myelodysplastic syndrome (MC-FludT.14/L): a randomised, non-inferiority, phase 3 trial. Lancet Haematol. 7, e28–e39 (2020).

    Article  PubMed  Google Scholar 

  241. British Society of Blood and Marrow Transplantation and Cellular Therapy (BSBMTCT). Indications Table. BSBMTCT https://bsbmtct.org/indications-table/ (2013).

  242. Hu, F. et al. Improving prediction accuracy in acute myeloid leukaemia: micro-environment, immune and metabolic models. Leukemia https://doi.org/10.1038/s41375-021-01377-0 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  243. Meers, S. et al. Monocytes are activated in patients with myelodysplastic syndromes and can contribute to bone marrow failure through CD40-CD40L interactions with T helper cells. Leukemia 21, 2411–2419 (2007).

    Article  CAS  PubMed  Google Scholar 

  244. Voso, M. T. et al. Why methylation is not a marker predictive of response to hypomethylating agents. Haematologica 99, 613–619 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  245. Estey, E. H. Epigenetics in clinical practice: the examples of azacitidine and decitabine in myelodysplasia and acute myeloid leukemia. Leukemia 27, 1803–1812 (2013).

    Article  CAS  PubMed  Google Scholar 

  246. Fandy, T. E. et al. Early epigenetic changes and DNA damage do not predict clinical response in an overlapping schedule of 5-azacytidine and entinostat in patients with myeloid malignancies. Blood 114, 2764–2773 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  247. Kantarjian, H. et al. Safety and efficacy of romiplostim in patients with lower-risk myelodysplastic syndrome and thrombocytopenia. J. Clin. Oncol. 28, 437–444 (2010).

    Article  CAS  PubMed  Google Scholar 

  248. Sekeres, M. A. et al. Subcutaneous or intravenous administration of romiplostim in thrombocytopenic patients with lower risk myelodysplastic syndromes. Cancer 117, 992–1000 (2011).

    Article  CAS  PubMed  Google Scholar 

  249. Fenaux, P. et al. Romiplostim monotherapy in thrombocytopenic patients with myelodysplastic syndromes: long-term safety and efficacy. Br. J. Haematol. 178, 906–913 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  250. Kantarjian, H. M. et al. Long-term follow-up for up to 5 years on the risk of leukaemic progression in thrombocytopenic patients with lower-risk myelodysplastic syndromes treated with romiplostim or placebo in a randomised double-blind trial. Lancet Haematol. 5, e117–e126 (2018).

    Article  PubMed  Google Scholar 

  251. Fenaux, P., Platzbecker, U. & Ades, L. How we manage adults with myelodysplastic syndrome. Br. J. Haematol. 189, 1016–1027 (2020).

    Article  CAS  PubMed  Google Scholar 

  252. Ades, L., Itzykson, R. & Fenaux, P. Myelodysplastic syndromes. Lancet 383, 2239–2252 (2014).

    Article  PubMed  Google Scholar 

  253. Aaronson, N. K. et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J. Natl Cancer Inst. 85, 365–376 (1993).

    Article  CAS  PubMed  Google Scholar 

  254. Stauder, R. et al. Patient-reported outcome measures in studies of myelodysplastic syndromes and acute myeloid leukemia: Literature review and landscape analysis. Eur. J. Haematol. 104, 476–487 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  255. Goswami, P. et al. Paper and electronic versions of HM-PRO, a novel patient-reported outcome measure for hematology: an equivalence study. J. Comp. Eff. Res. 8, 523–533 (2019).

    Article  PubMed  Google Scholar 

  256. Abel, G. A. et al. Prospective international validation of the quality of life in Myelodysplasia scale (QUALMS). Haematologica 101, 781–788 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  257. Oliva, E., Nobile, F. & Dimitrov, B. Development and validation of QOL-E© instrument for the assessment of health-related quality of life in myelodysplastic syndromes. Open Med. 8, 835–844 (2013).

    Article  Google Scholar 

  258. Smets, E. M., Garssen, B., Bonke, B. & De Haes, J. C. The multidimensional fatigue inventory (MFI) psychometric qualities of an instrument to assess fatigue. J. Psychosom. Res. 39, 315–325 (1995).

    Article  CAS  PubMed  Google Scholar 

  259. Mendoza, T. R. et al. The rapid assessment of fatigue severity in cancer patients: use of the brief fatigue inventory. Cancer 85, 1186–1196 (1999).

    Article  CAS  PubMed  Google Scholar 

  260. Ware, J. E. J. & Sherbourne, C. D. The MOS 36-item short-form health survey (SF-36): I. Conceptual framework and item selection. Med. Care 30, 473–483 (1992).

    Article  PubMed  Google Scholar 

  261. Ware, J. E., Kosinski, M. & Keller, S. D. A 12-item short-form health survey: construction of scales and preliminary tests of reliability and validity. Med. Care 34, 220–233 (1996).

    Article  PubMed  Google Scholar 

  262. EuroQol Group. EuroQol-a new facility for the measurement of health-related quality of life. Health Policy 16, 199–208 (1990).

    Article  Google Scholar 

  263. Abel, G. A. et al. Peri-transfusion quality-of-life assessment for patients with myelodysplastic syndromes. Transfusion 61, 2830–2836 (2021).

    Article  PubMed  Google Scholar 

  264. Steensma, D. P. et al. Common troublesome symptoms and their impact on quality of life in patients with myelodysplastic syndromes (MDS): results of a large internet-based survey. Leuk. Res. 32, 691–698 (2008).

    Article  PubMed  Google Scholar 

  265. Efficace, F. et al. Prevalence, severity and correlates of fatigue in newly diagnosed patients with myelodysplastic syndromes. Br. J. Haematol. 168, 361–370 (2015).

    Article  PubMed  Google Scholar 

  266. Oliva, E. N. et al. Lenalidomide in international prognostic scoring system low and intermediate-1 risk myelodysplastic syndromes with del(5q): an Italian phase II trial of health-related quality of life, safety and efficacy. Leuk. Lymphoma 54, 2458–2465 (2013).

    Article  CAS  PubMed  Google Scholar 

  267. Giesinger, J. M. et al. Health-related quality of life assessment in patients with Myelodysplastic syndromes: evidence from randomized clinical trials. Clin. Pract. Epidemiol. Ment. Health 17, 307–314 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  268. Barosi, G. & Gale, R. P. Is there expert consensus on expert consensus? Bone Marrow Transpl. 53, 1055–1060 (2018).

    Article  Google Scholar 

  269. Medeiros, B. C. et al. Isocitrate dehydrogenase mutations in myeloid malignancies. Leukemia 31, 272–281 (2017).

    Article  CAS  PubMed  Google Scholar 

  270. Thol, F. et al. IDH1 mutations in patients with myelodysplastic syndromes are associated with an unfavorable prognosis. Haematologica 95, 1668–1674 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  271. Jin, J. et al. Prognostic value of isocitrate dehydrogenase mutations in myelodysplastic syndromes: a retrospective cohort study and meta-analysis. PLoS ONE 9, e100206 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  272. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT04493164 (2020).

  273. DiNardo, C. D. et al. Targeted therapy with the mutant IDH2 inhibitor enasidenib for high-risk IDH2-mutant myelodysplastic syndrome. Blood Adv. https://doi.org/10.1182/bloodadvances.2022008378 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  274. DiNardo, C. D. et al. Durable remissions with ivosidenib in IDH1-mutated relapsed or refractory AML. N. Engl. J. Med. 378, 2386–2398 (2018).

    Article  CAS  PubMed  Google Scholar 

  275. Comont, T. et al. Eltrombopag for myelodysplastic syndromes or chronic myelomonocytic leukaemia with no excess blasts and thrombocytopenia: a French multicentre retrospective real-life study. Br. J. Haematol. 194, 336–343 (2021).

    Article  CAS  PubMed  Google Scholar 

  276. Vicente, A. et al. Eltrombopag monotherapy can improve hematopoiesis in patients with low to intermediate risk-1 myelodysplastic syndrome. Haematologica 105, 2785–2794 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  277. Mittelman, M. et al. Eltrombopag for advanced myelodysplastic syndromes or acute myeloid leukaemia and severe thrombocytopenia (ASPIRE): a randomised, placebo-controlled, phase 2 trial. Lancet Haematol. 5, e34 (2018). This paper reports a phase III study of eltrombopag in the treatment of advanced MDS.

    Article  PubMed  Google Scholar 

  278. US Food and Drug Administration. Drugs@FDA: Prescribing Information for Promacta. US Food and Drug Administration https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022291s019lbl.pdf (2017).

  279. Matlung, H. L., Szilagyi, K., Barclay, N. A. & van den Berg, T. K. The CD47-SIRPα signaling axis as an innate immune checkpoint in cancer. Immunol. Rev. 276, 145–164 (2017).

    Article  CAS  PubMed  Google Scholar 

  280. Willingham, S. B. et al. The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors. Proc. Natl Acad. Sci. USA 109, 6662–6667 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  281. Pang, W. W. et al. Hematopoietic stem cell and progenitor cell mechanisms in myelodysplastic syndromes. Proc. Natl Acad. Sci. USA 110, 3011–3016 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  282. Sallman, D. A. et al. Magrolimab in combination with azacitidine for untreated higher-risk myelodysplastic syndromes (HR-MDS): 5F9005 phase 1b study results. J. Clin. Oncol. 40, 7017 (2022).

    Article  Google Scholar 

  283. Garcia, J. S. et al. Safety, efficacy, and patient-reported outcomes of venetoclax in combination with azacitidine for the treatment of patients with higher-risk myelodysplastic syndrome: a phase 1b study. Blood 136, 55–57 (2020).

    Article  Google Scholar 

  284. Zeidan, A. M. et al. A phase 1b study evaluating the safety and efficacy of venetoclax as monotherapy or in combination with azacitidine for the treatment of relapsed/refractory myelodysplastic syndrome. Blood 134, 565–565 (2019).

    Article  Google Scholar 

  285. DiNardo, C. D. et al. Molecular patterns of response and treatment failure after frontline venetoclax combinations in older patients with AML. Blood 135, 791–803 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

Y.L. is supported, in part, by Sun Yat-sen University Cancer Center Start-Up Funding (No. 201603), the National Natural Science Foundation of China (81873428) and the Programme for Guangdong Introducing Innovative and Entrepreneurial Teams (2017ZT07S096). R.P.G. acknowledges support from the National Institute of Health Research (NIHR) Biomedical Research Centre funding scheme. Y.L. and R.P.G. acknowledge support funding from the Ministry of Science and Technology of China (84000-51200002). E. Hellström-Lindberg (Karolinska Institute) and D. Steensma (Novartis Corp.) kindly reviewed the typescript.

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Introduction (Y.L., R.P.G. and H.L.); Epidemiology (H.L. and R.P.G.); Mechanisms/pathophysiology (R.P.G., F.H. and M.A.S.); Diagnosis, screening and prevention (M.A.S., H.L., Y.L. and R.P.G.); Management (Y.L., M.A.S. and R.P.G.); Quality of life (Y.L., R.P.G. and F.H.); Outlook (Y.L. and R.P.G.); Overview of the Primer (M.A.S., R.P.G. and Y.L.).

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Correspondence to Yang Liang.

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Competing interests

R.P.G. is a consultant to NexImmune Inc. and Ananexa Pharma Ascentage Pharm Group, Antengene Biotech LLC; Medical Director, FFF Enterprises Inc.; partner, AZAC Inc.; Board of Directors, Russian Foundation for Cancer Research Support; and Scientific Advisory Board: StemRad Ltd. M.A.S. is on advisory boards for BMS, Novartis, Syros and Kurome. Y.L., H.L. and F.H. declare no competing interests.

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Li, H., Hu, F., Gale, R.P. et al. Myelodysplastic syndromes. Nat Rev Dis Primers 8, 74 (2022). https://doi.org/10.1038/s41572-022-00402-5

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