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CHRONIC MYELOPROLIFERATIVE NEOPLASMS

Myelodysplastic syndrome/myeloproliferative neoplasm overlap syndromes: a practical guide to diagnosis and management

Leukemia volume 39, pages 1311–1324 (2025)Cite this article

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Abstract

Myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) overlap syndromes are a rare group of biologically and clinically connected hematologic malignancies that includes chronic myelomonocytic leukemia (CMML), the most common subtype, as well as atypical chronic myeloid leukemia, MDS/MPN with SF3B1 and thrombocytosis, and MDS/MPN, not otherwise specified. Given their rarity and overlapping clinical features, accurate diagnosis and risk stratification presents a significant challenge. Therapeutic approaches are largely borrowed from either MDS or MPN and the only curative option for appropriate patients is allogeneic stem cell transplantation. Recent advances have started to uncover the pathobiologic basis for these diseases, leading to novel clinical trials for MDS/MPN overlap syndromes, in particular CMML. This review is a practical guide for the diagnosis and management of MDS/MPN overlap syndromes and presents novel therapeutics being specifically designed for these diseases to improve their historically poor outcomes.

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Fig. 1: Overview of MDS/MPN overlap syndromes.
Fig. 2: Transplant decisions in MDS/MPN overlap syndromes.

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Acknowledgements

The authors would like to acknowledge Jill Gregory for the creation of Fig. 1.

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Authors and Affiliations

  1. Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Douglas Tremblay

  2. Massachusetts General Hospital, Boston, MA, USA

    Robert P. Hasserjian

  3. Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Raajit K. Rampal

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  2. Robert P. Hasserjian
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DT, RPH and RKR wrote the manuscript. All authors approved the final version of the manuscript.

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Correspondence to Douglas Tremblay.

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Competing interests

DT receives contracted research funding paid to his institution from Sobi, Sumitomo, Cogent Biosciences and Gilead and consulting fees from Sobi, AbbVie, Pharmaessentia, Sierra Oncology, GSK and Cogent Biosciences. RKR receives contracted research funding pain to his institution from Constellation pharmaceuticals, Ryvu, Sumitomo, Zentalis and Stemline Therapeutics and consulting fees from Incyte Corporation, Celgene/BMS, Blueprint, Abbvie, CTI, Stemline, Galecto, Pharmaessentia, Jubilant, Constellation/Morphosys, Sierra Oncology/GSK, Protagonist, Cogent, Sumitomo Dainippon, Kartos, Servier, Zentalis, Karyopharm. RPH declares no relevant conflicts of interest.

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Tremblay, D., Hasserjian, R.P. & Rampal, R.K. Myelodysplastic syndrome/myeloproliferative neoplasm overlap syndromes: a practical guide to diagnosis and management. Leukemia 39, 1311–1324 (2025). https://doi.org/10.1038/s41375-025-02620-8

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