Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

MYELODYSPLASTIC SYNDROME

Marrow ring sideroblasts are highly predictive for TP53 mutation in MDS with excess blasts

Leukemia volume 36, pages 1189–1192 (2022)Cite this article

Subjects

TO THE EDITOR,

Myelodysplastic syndrome with ring sideroblasts (MDS-RS) is now defined by the World Health Organization (WHO) as RS ≥ 15% or ≥5% with associated SF3B1 mutation and no excess blasts [1]. The update in classification was based on the high prevalence of SF3B1 mutations in MDS with ring sideroblasts with 65–85% of patients with RARS and RCMD-RS harboring mutations [2,3,4]. SF3B1 mutant MDS also represents a distinct disease subtype hallmarked by ineffective erythropoiesis and favorable prognosis [2]. The international workup group for the Prognosis of MDS (IWG-PM) recently proposed SF3B1-mt MDS as a distinct molecular subtype for future MDS classification, which has been subsequently validated [5, 6]. However, less is known regarding SF3B1-wild type RS patients and patients with RS and excess blasts (EB). Therefore, in this study, we performed large scale genetic profiling to better characterize MDS with RS, focusing on SF3B1-wt patient, MDS with EB and implications of molecular subsets, particularly TP53.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Molecular characterization and survival differences in MDS with ring sideroblasts ≥5%.

References

  1. Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127:2391–405.

    Article  CAS  Google Scholar 

  2. Malcovati L, Karimi M, Papaemmanuil E, Ambaglio I, Jadersten M, Jansson M, et al. SF3B1 mutation identifies a distinct subset of myelodysplastic syndrome with ring sideroblasts. Blood. 2015;126:233–41.

    Article  CAS  Google Scholar 

  3. Yoshida K, Sanada M, Shiraishi Y, Nowak D, Nagata Y, Yamamoto R, et al. Frequent pathway mutations of splicing machinery in myelodysplasia. Nature 2011;478:64–9.

    Article  CAS  Google Scholar 

  4. 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;365:1384–95.

    Article  CAS  Google Scholar 

  5. Malcovati L, Stevenson K, Papaemmanuil E, Neuberg D, Bejar R, Boultwood J, et al. SF3B1-mutant MDS as a distinct disease subtype: a proposal from the International Working Group for the Prognosis of MDS. Blood 2020;136:157–70.

    Article  CAS  Google Scholar 

  6. Komrokji RS, Volpe VO, Chan O, Al Ali NH, Swoboda DM, Kuykendall AT, et al. Validation of the International Working Group Proposal for SF3B1 mutant myelodysplastic syndromes. Blood. 2021;138:989–92.

  7. 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;364:2496–506.

    Article  CAS  Google Scholar 

  8. Haferlach T, Nagata Y, Grossmann V, Okuno Y, Bacher U, Nagae G, et al. Landscape of genetic lesions in 944 patients with myelodysplastic syndromes. Leukemia 2014;28:241–7.

    Article  CAS  Google Scholar 

  9. Haase D, Stevenson KE, Neuberg D, Maciejewski JP, Nazha A, Sekeres MA, et al. TP53 mutation status divides myelodysplastic syndromes with complex karyotypes into distinct prognostic subgroups. Leukemia 2019;33:1747–58.

    Article  CAS  Google Scholar 

  10. Sallman DA. The Problem of TP53-Mutant MDS/AML. Clin Lymphoma Myeloma Leuk. 2020;20(Suppl 1):S65–S6.

    Article  Google Scholar 

  11. Mufti GJ, Bennett JM, Goasguen J, Bain BJ, Baumann I, Brunning R, et al. Diagnosis and classification of myelodysplastic syndrome: International Working Group on Morphology of myelodysplastic syndrome (IWGM-MDS) consensus proposals for the definition and enumeration of myeloblasts and ring sideroblasts. Haematologica 2008;93:1712–7.

    Article  Google Scholar 

  12. Sallman DA, DeZern AE, Garcia-Manero G, Steensma DP, Roboz GJ, Sekeres MA, et al. Eprenetapopt (APR-246) and azacitidine in TP53-mutant myelodysplastic syndromes. J Clin Oncol. 2021;39:1584–94.

  13. Sallman DA, Al Malki M, Asch AS, Lee DJ, Kambhampati S, Donnellan WB, et al. Tolerability and efficacy of the first-in-class anti-CD47 antibody magrolimab combined with azacitidine in MDS and AML patients: Phase Ib results. J Clin Oncol. 2020;38(15_suppl):7507.

  14. Hunter AM, Sallman DA. Targeting TP53 mutations in myelodysplastic syndromes. Hematol Oncol Clin North Am. 2020;34:421–40.

    Article  Google Scholar 

  15. Sallman D, Asch AS, Kambhampati S, Malki M, Zeidner JF, Donnellan W, et al. The first-in-class anti-CD47 antibody magrolimab combined with azacitidine is well-tolerated and effective in AML patients: phase 1b results. Blood. 2019;134:569.

Download references

Author information

Authors and Affiliations

  1. Department of Malignant Hematology, H. Lee Moffitt Cancer Center, Tampa, FL, USA

    David M. Swoboda, Onyee Chan, Najla Al Ali, Andrew T. Kuykendall, Chetasi Talati, Kendra L. Sweet, Jeffrey E. Lancet, Eric Padron, Rami S. Komrokji & David A. Sallman

  2. Tampa General Hospital Cancer Institute, Tampa, FL, USA

    David M. Swoboda

  3. Department of Hematopathology and Molecular Diagnostics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Rashmi Kanagal-Shamanna

  4. Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA

    Andrew M. Brunner

  5. Department of Hematology, CHU of Nice, Nice, France

    Thomas Cluzeau

  6. Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, United States

    Guillermo Montalban-Bravo & Guillermo Garcia-Manero

  7. Department of Medicine, University of South Florida, Tampa, FL, USA

    Quinto J. Gesiotto

  8. Department of Internal Medicine, Mass General Brigham Salem Hospital, Boston, MA, USA

    Alexander Gavralidis

  9. Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA

    Anthony M. Hunter

  10. Department of Hematology and Medical Oncology, Weill Cornell Medical College, New York, NY, USA

    Jung-Hoon Lee

  11. Department of Pathology, H. Lee Moffitt Cancer Center, Tampa, FL, USA

    Mohammad Hussaini & Jinming Song

Authors
  1. David M. Swoboda
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rashmi Kanagal-Shamanna
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Andrew M. Brunner
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Thomas Cluzeau
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Onyee Chan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Najla Al Ali
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Guillermo Montalban-Bravo
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Quinto J. Gesiotto
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Alexander Gavralidis
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Anthony M. Hunter
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Jung-Hoon Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Andrew T. Kuykendall
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Chetasi Talati
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Kendra L. Sweet
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Jeffrey E. Lancet
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Eric Padron
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Mohammad Hussaini
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Jinming Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Guillermo Garcia-Manero
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Rami S. Komrokji
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. David A. Sallman
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

DMS and DAS designed the study, performed statistical analysis, and wrote the manuscript. RKS, AMB, TC, OC, NAA, GMB, QJG, AG, AMH, JL, ATK, CT, KS, JEL, EP, MH, JS, GGM, and RSK contributed patients and/or collected data and/or participated in the interpretation of results. All authors approved final manuscript.

Corresponding author

Correspondence to David A. Sallman.

Ethics declarations

Competing interests

DMS, RKS, TC, OC, NAA, GMB, QJG, AG, AMH, JL, JS, and GGM declare no conflict of interest. AMB has done consulting for Novartis, BMS, Agios, Acceleron, and Takeda. ATK has done consulting for Abbvie, Blueprint, Celgene/BMS, Incyte, Novartis, PharmaEssentia, Protagonist, CTI Biopharma and has been part of a speaker’s bureau for Blueprint and Novartis. He receives research support from Sierra, Protagonist, and Prelude. CT is on advisory boards for Abbvie, BMS, Celgene, Daiichi Sankyo, Pfizer, and Novartis and has been part of a speaker’s bureau for Astellas, BMS, and Jazz. KS is on advisory committees for Arog, BMS, Gilead and Novartis. She has received research funding from Incyte and has received Honoraria from Stemline and Astellas. JEL has done consulting for AbbVie, Agios, Astella, Daiichi Sankyo, ElevateBio, Jazz, and Takeda and received Honoria from Agios. EP obtains research funding from Incyte, Kura Oncology, and BMS and has received Honoraria from Taiho. MH has done consulting and received honoraria from Adaptive Biotechnology, Stemline, Amgen, Seattle Genetics, BMS, Boston Biomedical, Decibio, Wells Fargo, Pivot and Blueprint Medicine. GGM RSK has been part of a speaker’s bureau for Jazz and BMS and received honoraria from JAZZ, BMS, Abbvie, Acceleron, Novartis, and Geron. DAS has received research funding from Aprea and Jazz, done consulting for AbbVie, Agios, Aprea, BMS, Incyte, Intellia, Kite, Magenta, Novartis, Shattuck Labs, and Takeda and part of a speaker’s bureau for BMS, Incyte. None of these relationships were related to the development of this manuscript.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Swoboda, D.M., Kanagal-Shamanna, R., Brunner, A.M. et al. Marrow ring sideroblasts are highly predictive for TP53 mutation in MDS with excess blasts. Leukemia 36, 1189–1192 (2022). https://doi.org/10.1038/s41375-021-01486-w

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41375-021-01486-w

Search

Advanced search

Quick links