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Molecular basis of myelodysplastic syndromes

Leukemia Supplements volume 1, pages S35–S36 (2012)Cite this article

Abstract

Myelodysplastic syndromes (MDS) are myeloid neoplasms characterized by dysplasia in one or more cell lines, ineffective hematopoiesis and variable risk of progression to acute myeloid leukemia. In the past few years, important steps have been taken in characterizing the molecular basis of MDS. More recently, somatic mutations in genes encoding core components of the RNA splicing machinery have been detected in high proportions of MDS patients, and are shown to be founding mutations in many instances. These mutations have different clinical significance, and their incorporation into current stratification systems might improve risk assessment in MDS.

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References

  1. Cazzola M, Malcovati L . Myelodysplastic syndromes--coping with ineffective hematopoiesis. N Engl J Med 2005; 352: 536–538.

    Article  CAS  Google Scholar 

  2. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. IARC: Lyon, 2008.

    Google Scholar 

  3. Brunning RD, Orazi A, Germing U, Le Beau MM, Porwit A, Bauman I et al. Myelodysplastic syndromes/neoplasms, overview. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al. (eds). WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. IARC: Lyon, 2008, pp 88–93.

    Google Scholar 

  4. Malcovati L, Della Porta MG, Pascutto C, Invernizzi R, Boni M, Travaglino E et al. Prognostic factors and life expectancy in myelodysplastic syndromes classified according to WHO criteria: a basis for clinical decision making. J Clin Oncol 2005; 23: 7594–7603.

    Article  Google Scholar 

  5. Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 1997; 89: 2079–2088.

    Article  CAS  Google Scholar 

  6. Malcovati L, Germing U, Kuendgen A, Della Porta MG, Pascutto C, Invernizzi R et al. Time-dependent prognostic scoring system for predicting survival and leukemic evolution in myelodysplastic syndromes. J Clin Oncol 2007; 25: 3503–3510.

    Article  Google Scholar 

  7. Della Porta MG, Malcovati L, Strupp C, Ambaglio I, Kuendgen A, Zipperer E et al. Risk stratification based on both disease status and extra-hematologic comorbidities in patients with myelodysplastic syndrome. Haematologica 2011; 96: 441–449.

    Article  Google Scholar 

  8. Delhommeau F, Dupont S, Della Valle V, James C, Trannoy S, Masse A et al. Mutation in TET2 in myeloid cancers. N Engl J Med 2009; 360: 2289–2301.

    Article  Google Scholar 

  9. Langemeijer SM, Kuiper RP, Berends M, Knops R, Aslanyan MG, Massop M et al. Acquired mutations in TET2 are common in myelodysplastic syndromes. Nat Genet 2009; 41: 838–842.

    Article  CAS  Google Scholar 

  10. Smith AE, Mohamedali AM, Kulasekararaj A, Lim Z, Gaken J, Lea NC et al. Next-generation sequencing of the TET2 gene in 355 MDS and CMML patients reveals low-abundance mutant clones with early origins, but indicates no definite prognostic value. Blood 2010; 116: 3923–3932.

    Article  CAS  Google Scholar 

  11. Bejar R, Stevenson K, Abdel-Wahab O, Galili N, Nilsson B, Garcia-Manero G et al. Clinical effect of point mutations in myelodysplastic syndromes. N Engl J Med 2011; 364: 2496–2506.

    Article  CAS  Google Scholar 

  12. Yoshida K, Sanada M, Shiraishi Y, Nowak D, Nagata Y, Yamamoto R et al. Frequent pathway mutations of splicing machinery in myelodysplasia. Nature 2011; 478: 64–69.

    Article  CAS  Google Scholar 

  13. Papaemmanuil E, Cazzola M, Boultwood J, Malcovati L, Vyas P, Bowen D et al. Somatic SF3B1 mutation in myelodysplasia with ring sideroblasts. N Engl J Med 2011; 365: 1384–1395.

    Article  CAS  Google Scholar 

  14. Graubert TA, Shen D, Ding L, Okeyo-Owuor T, Lunn CL, Shao J et al. Recurrent mutations in the U2AF1 splicing factor in myelodysplastic syndromes. Nat Genet 2012; 44: 53–57.

    Article  CAS  Google Scholar 

  15. Makishima H, Visconte V, Sakaguchi H, Jankowska AM, Abu Kar S, Jerez A et al. Mutations in the spliceosome machinery, a novel and ubiquitous pathway in leukemogenesis. Blood 2012; 119: 3203–3210.

    Article  CAS  Google Scholar 

  16. Damm F, Kosmider O, Gelsi-Boyer V, Renneville A, Carbuccia N, Hidalgo-Curtis C et al. Mutations affecting mRNA splicing define distinct clinical phenotypes and correlate with patient outcome in myelodysplastic syndromes. Blood 2012; 119: 3211–3218.

    Article  CAS  Google Scholar 

  17. Thol F, Kade S, Schlarmann C, Loffeld P, Morgan M, Krauter J et al. Frequency and prognostic impact of mutations in SRSF2, U2AF1, and ZRSR2 in patients with myelodysplastic syndromes. Blood 2012; 119: 3578–3584.

    Article  CAS  Google Scholar 

  18. Malcovati L, Papaemmanuil E, Bowen DT, Boultwood J, Della Porta MG, Pascutto C et al. Clinical significance of SF3B1 mutations in myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms. Blood 2011; 118: 6239–6246.

    Article  CAS  Google Scholar 

  19. Hyjek E, Vardiman JW . Myelodysplastic/myeloproliferative neoplasms. Semin Diagn Pathol 2011; 28: 283–297.

    Article  Google Scholar 

  20. Malcovati L, Della Porta MG, Pietra D, Boveri E, Pellagatti A, Galli A et al. Molecular and clinical features of refractory anemia with ringed sideroblasts associated with marked thrombocytosis. Blood 2009; 114: 3538–3545.

    Article  CAS  Google Scholar 

  21. Muramatsu H, Makishima H, Maciejewski JP . Chronic myelomonocytic leukemia and atypical chronic myeloid leukemia: novel pathogenetic lesions. Semin Oncol 2012; 39: 67–73.

    Article  CAS  Google Scholar 

  22. Cazzola M, Malcovati L, Invernizzi R . Myelodysplastic/myeloproliferative neoplasms. Hematol Am Soc Hematol Educ Prog 2011; 2011: 264–272.

    Article  Google Scholar 

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Acknowledgements

MC has received grant support from Associazione Italiana per la Ricerca sul Cancro (AIRC).

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Authors and Affiliations

  1. Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo and University of Pavia, Pavia, Italy

    M Cazzola

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  1. M Cazzola
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Correspondence to M Cazzola.

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The author declares no conflict of interest.

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This article was published as part of a supplement that was supported by Novartis, MSD Italia, Roche, Celgene, GlaxoSmithKline, Sanofi, Gilead, Adienne, Italfarmaco, Pierre Fabre Pharmaceuticals with an unrestricted educational contribution to AREO—Associazione Ricerche Emato-Oncologiche (Genoa) and AMS—Associazione Malattie del Sangue (Milan) for the purpose of advancing research in acute and chronic leukemia.

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Cazzola, M. Molecular basis of myelodysplastic syndromes. Leukemia Suppl 1 (Suppl 2), S35–S36 (2012). https://doi.org/10.1038/leusup.2012.20

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