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.

  • Correspondence
  • Published:

MYELODYSPLASTIC NEOPLASMS

Differences in classification schemata for myelodysplastic/myeloproliferative overlap neoplasms

Leukemia volume 36, pages 2934–2938 (2022)Cite this article

Subjects

This article has been updated

Recently, the World Health Organization (WHO) Classification and the International Consensus Classification (ICC) systems for hematological neoplasms have been published [1, 2]. While there have been some critical updates which further distinguish and clarify categories of hematological neoplasms, we write here to highlight important nuances in each classification schema for myelodysplastic/myeloproliferative neoplasms (MDS/MPN). Discussing these differences is important to avoid any potential to adversely impact the interpretation of bone marrow (BM) results, enrollment to and response assessment in clinical trials, insurance claims and reimbursement, revenue coding systems (e.g., ICD-10) and, ultimately, patient care. The first international workshop on MDS (iwMDS-2022) was conducted in Miami, FL, in July 2022, and provided a forum to discuss each of these recently updated MDS/MPN classification schema. Here, we highlight key differences for the clinical community and provide suggestions on how we can work to enhance consistency moving forward.

The 2016 WHO criteria formally included 5 neoplasms within the MDS/MPN overlap neoplasm category [3]. These included chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia (aCML), BCR::ABL1 negative, MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T), MDS/MPN- Unclassifiable (MDS/MPN-U) and juvenile myelomonocytic leukemia (JMML). In the current classification updates, both the WHO and the ICC have eliminated JMML from the overlap neoplasms category.

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

Change history

  • 18 November 2022

    The super title has been corrected.

References

  1. Arber DA, Orazi A, Hasserjian RP, Borowitz MJ, Calvo KR, Kvasnicka HM, et al. International consensus classification of myeloid neoplasms and acute leukemia: integrating morphological, clinical, and genomic data. Blood. 2022;140:1200–28.

  2. Khoury JD, Solary E, Abla O, Akkari Y, Alaggio R, Apperley JF, et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms. Leukemia. 2022;36:1703–19.

    Article  PubMed  PubMed Central  Google Scholar 

  3. 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  PubMed  Google Scholar 

  4. Patnaik MM, Tefferi A. Chronic myelomonocytic leukemia: 2022 update on diagnosis, risk stratification and management. Am J Hematol. 2020;95:97–115.

  5. Binder M, Carr RM, Lasho TL, Finke CM, Mangaonkar AA, Pin CL, et al. Oncogenic gene expression and epigenetic remodeling of cis-regulatory elements in ASXL1-mutant chronic myelomonocytic leukemia. Nat Commun. 2022;13:1434.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Carr RM, Vorobyev D, Lasho T, Marks DL, Tolosa EJ, Vedder A, et al. RAS mutations drive proliferative chronic myelomonocytic leukemia via a KMT2A-PLK1 axis. Nat Commun. 2021;12:2901.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Loghavi S, Sui D, Wei P, Garcia-Manero G, Pierce S, Routbort MJ, et al. Validation of the 2017 revision of the WHO chronic myelomonocytic leukemia categories. Blood Adv. 2018;2:1807–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Patnaik MM, Timm MM, Vallapureddy R, Lasho TL, Ketterling RP, Gangat N, et al. Flow cytometry based monocyte subset analysis accurately distinguishes chronic myelomonocytic leukemia from myeloproliferative neoplasms with associated monocytosis. Blood Cancer J. 2017;7:e584.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Wagner-Ballon O, Bettelheim P, Lauf J, Bellos F, Della Porta M, Travaglino E, et al. ELN iMDS flow working group validation of the monocyte assay for chronic myelomonocytic leukemia diagnosis by flow cytometry. Cytometry B Clin Cytom. 2021. https://doi.org/10.1002/cyto.b.22054.

  10. Pophali PA, Timm MM, Mangaonkar AA, Shi M, Reichard K, Tefferi A, et al. Practical limitations of monocyte subset repartitioning by multiparametric flow cytometry in chronic myelomonocytic leukemia. Blood Cancer J. 2019;9:65.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Solary E, Wagner-Ballon O, Selimoglu-Buet D. Incorporating flow cytometry and next-generation sequencing in the diagnosis of CMML. Are we ready for prime? Best Pr Res Clin Haematol. 2020;33:101134.

    Article  Google Scholar 

  12. Tarfi S, Badaoui B, Freynet N, Morabito M, Lafosse J, Toma A, et al. Disappearance of slan-positive non-classical monocytes for diagnosis of chronic myelomonocytic leukemia with associated inflammatory state. Haematologica. 2019;haematol.2019.219782.

  13. Gotlib J, Maxson JE, George TI, Tyner JW. The new genetics of chronic neutrophilic leukemia and atypical CML: implications for diagnosis and treatment. Blood. 2013;122:1707–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Mangaonkar AA, Swoboda DM, Lasho TL, Finke C, Ketterling RP, Reichard KK, et al. Genomic stratification of myelodysplastic/myeloproliferative neoplasms, unclassifiable: sorting through the unsorted. Leukemia. 2021;35:3329–3333.

  15. Bezerra ED, Lasho TL, Finke CM, Saliba AN, Elliott MA, Pardanani AD, et al. CSF3R T618I mutant chronic myelomonocytic leukemia (CMML) defines a proliferative CMML subtype enriched in ASXL1 mutations with adverse outcomes. Blood Cancer J. 2021;11:54.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Mangaonkar AA, Swoboda DM, Coltro G, Lasho TL, Novotny PJ, Pophali P, et al. Clinicopathologic characteristics, prognostication and treatment outcomes for myelodysplastic/myeloproliferative neoplasm, unclassifiable (MDS/MPN-U): Mayo Clinic-Moffitt Cancer Center study of 135 consecutive patients. Leukemia. 2020;34:656–61.

    Article  PubMed  Google Scholar 

  17. Patnaik MM, Hanson CA, Sulai NH, Hodnefield JM, Knudson RA, Ketterling RP, et al. Prognostic irrelevance of ring sideroblast percentage in World Health Organization defined myelodysplastic syndromes without excess blasts. Blood. 2012;119:5674–7.

  18. Palomo L, Meggendorfer M, Hutter S, Twardziok S, Adema V, Fuhrmann I, et al. Molecular landscape and clonal architecture of adult myelodysplastic/myeloproliferative neoplasms. Blood. 2020;136:1851–62.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA

    Mrinal M. Patnaik

  2. Section of Hematology, Department of Internal Medicine, Yale University School of Medicine and Yale Cancer Center, New Haven, CT, USA

    Amer M. Zeidan

  3. Malignant Hematology, Moffitt Cancer Center, Tampa, FL, USA

    Eric Padron, David A. Sallman, Rami Komrokji & Zhuoer Xie

  4. Department of Hematology, University of Leipzig, Leipzig, Germany

    Uwe Platzbecker

  5. Division of Hematologic Malignancies; Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA

    Amy E. DeZern

  6. Division of Hematology and Oncology, Moores Cancer Center, UC San Diego, La Jolla, CA, USA

    Rafael Bejar

  7. Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA

    Mikkael Sekeres & Justin Taylor

  8. National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    Richard F. Little, Nina Kim & Christopher S. Hourigan

  9. Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Jan P. Bewersdorf

  10. Division of Hematology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA

    Tae Kon. Kim & Michael Savona

  11. Humanitas Clinical and Research Center & Humanitas University, Department of Biomedical Sciences, Milan, Italy

    Matteo G. Dela Porta

  12. Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA

    Maximilian Stahl

  13. Novartis Institute of Blood Research, Boston, MA, USA

    David Steensma

  14. Departments of Pathology & Laboratory Medicine, Yale University School of Medicine and Yale Cancer Center, New Haven, CT, USA

    Mina L. Xu

  15. Section of Hematology/Oncology, the University of Chicago Medicine, Chicago, IL, USA

    Olatoyosi Odenike

  16. Leukemia Program, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA

    Hetty Carraway

  17. Hôpital St Louis, Assistance Publique Hôpitaux de Paris, and Université Paris Cité, Paris, France

    Pierre Fenaux

  18. Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA

    Aziz Nazha

  19. Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA

    Sanam Loghavi

  20. Department of Pathology, Massachusetts General Hospital, Boston, MA, USA

    Robert Hasserjian

  21. Department of Medicine, Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA

    John M. Bennett

Authors
  1. Mrinal M. Patnaik
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Amer M. Zeidan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eric Padron
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Uwe Platzbecker
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. David A. Sallman
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Amy E. DeZern
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Rafael Bejar
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mikkael Sekeres
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Justin Taylor
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Richard F. Little
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Jan P. Bewersdorf
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Tae Kon. Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Nina Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Christopher S. Hourigan
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Matteo G. Dela Porta
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Maximilian Stahl
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. David Steensma
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Mina L. Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Olatoyosi Odenike
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Hetty Carraway
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Pierre Fenaux
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Aziz Nazha
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Rami Komrokji
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. Sanam Loghavi
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. Zhuoer Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

  26. Robert Hasserjian
    View author publications

    You can also search for this author in PubMed Google Scholar

  27. Michael Savona
    View author publications

    You can also search for this author in PubMed Google Scholar

  28. John M. Bennett
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

MP and JB wrote the initial draft of the manuscript. All authors were involved in writing, reviewing, and editing the manuscript and approved the final version for submission.

Corresponding author

Correspondence to Mrinal M. Patnaik.

Ethics declarations

Competing interests

The first international workshop on MDS was planned by an independent scientific steering committee. The meeting was supported by unrestricted educational grants from Gilead, Novartis, BMS, Syros, Geron and Karyopharm to Magdalen Medical/VJHemOnc. The International Consortium for MDS (icMDS); a panel of international experts with a focus on preclinical and clinical MDS research including basic scientists, medical oncologist/hematologists, and pathologists convened in the 1st international workshop on MDS, which was held in Miami, FL in June 2022. This manuscript was drafted by a core group with iterative review by all authors. The meeting sponsors were not involved in the development of this manuscript. All authors developed and approved this manuscript in their personal capacity and their views do not necessarily represent/reflect that of their employers. MMP, EP, SL, UP, DS, RB are authors on WHO classification. MS, RH and OO are authors on the ICC system. RK worked with WHO on the MDS classification, but not on MDS/MPN overlap neoplasms. MMP has received research funding from Kura Oncology and Stemline Pharmaceuticals. AMZ is a Leukemia and Lymphoma Society Scholar in Clinical Research and received research funding (institutional) from Celgene/BMS, Abbvie, Astex, Pfizer, Medimmune/AstraZeneca, Boehringer-Ingelheim, Cardiff oncology, Incyte, Takeda, Novartis, Aprea, and ADC Therapeutics. AMZ participated in advisory boards, and/or had a consultancy with and received honoraria from AbbVie, Otsuka, Pfizer, Celgene/BMS, Jazz, Incyte, Agios, Boehringer-Ingelheim, Novartis, Acceleron, Astellas, Daiichi Sankyo, Cardinal Health, Taiho, Seattle Genetics, BeyondSpring, Cardiff Oncology, Takeda, Ionis, Amgen, Janssen, Epizyme, Syndax, Gilead, Kura, Chiesi, ALX Oncology, BioCryst, Notable, Orum, and Tyme. AMZ served on clinical trial committees for Novartis, Abbvie, Gilead, BioCryst, Abbvie, ALX Oncology, Geron and Celgene/BMS. AD received consulting fees from Geron, Bristol-Myers Squibb, Novartis, Takeda, Geron, Taiho, CTI Biopharma, Gilead. RB conflicts of interest include: Aptose Biosciences - employment and equity, Gilead - data safety monitoring committees chair, Epizyme - data safety monitoring committee chair, BMS - honoraria, research funding, Takeda - research funding. RK consulted for Abbvie: Speaker Bureau, Advisory board; BMS: Research Grant, Advisory board; CTI biopharma: Speaker Bureau, Advisory board; Geron: Consultancy; Jazz: Speaker Bureau, Advisory board. Novartis: Advisory board; Pharma Essentia: Speaker Bureau, Advisory board; Servio: Speaker Bureau, Advisory board; Taiho: Advisory board. MS has participated in advisory Boards for BMS, Kurome and Novartis. JT has participated in advisory board for Kyropharm. TKK has received funding from Nextcure, that is not relevant to this manuscript. TKK is a consultant for Agenus and Immunobiome. MS consulted for Curis Oncology and Boston Consulting; served on the advisory board for Novartis, Kymera and Sierra Oncology; and participated in GME activity for Novartis, Curis Oncology, Haymarket Media and Clinical care options (CCO) DS has the following COI: Novartis (employment) and Bluebird and Arrowhead (Stock Ownership). MX participated in advisory boards and/or had a consultancy with and received honoraria from Seattle Genetics, Pure Marrow and Blueprint Medicines. PF has received honoraria and, as Groupe Francophone des Myelodysplasie’s chairperson, research support from: BMS/Celgene, Novartis, Janssen, Jazz, Abbvie. AN owns stocks in Amazon and Incyte. Employee at Incyte Pharmaceutical. SL has received research funding from Amgen and Astellas, has participated in advisory Boards for Abbvie and Guidepoint; has served as a consultant for Gerson Lehrman Group and QualWorld, and has stock ownership in Abbvie. OO has served on the advisory board of Bristol-Myers Squibb, Celgene, Novartis, Taiho and Kymera Therapeutics; serves on a DSMB for Threadwell Therapeutics and received research funding (institutional) from ABBVIE, Agios, Aprea, Astex, Astra Zeneca, Bristol Myers Squibb, Celgene, CTI, Daiichi, Incyte, Janssen, Kartos, Loxo, Novartis, NS-Pharma and Oncotherapy Sciences.

Additional information

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Patnaik, M.M., Zeidan, A.M., Padron, E. et al. Differences in classification schemata for myelodysplastic/myeloproliferative overlap neoplasms. Leukemia 36, 2934–2938 (2022). https://doi.org/10.1038/s41375-022-01754-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41375-022-01754-3

Search

Advanced search

Quick links