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The co-occurrence of driver mutations in chronic myeloproliferative neoplasms

Annals of Hematology volume 97, pages 2071–2080 (2018)Cite this article

Abstract

Myeloproliferative neoplasms (MPNs) are clonal disorders characterized by proliferation of one or more elements of the myeloid lineage. Key genetic aberrations include the BCR-ABL1 gene rearrangement in Philadelphia chromosome-positive chronic myelogenous leukemia (CML) and JAK2/MPL/CALR aberrations in Philadelphia chromosome-negative MPNs. While thought to be mutually exclusive, occasional isolated reports of coexistence of BCR-ABL1 and JAK2, and JAK2 with MPL or CALR aberrations have been described. Given the paucity of data, clinical characteristics and outcome of patients harboring concurrent Philadelphia-positive and Philadelphia-negative mutations or dual Philadelphia-negative driver mutations have not been systematically evaluated, and their clinical relevance is largely unknown. It is difficult to determine the true relevance of co-existing driver mutations on outcomes given the rarity of its occurrence. In this case series, we describe those patients who had dual driver mutations detected at any point during the course of their disease and characterized their clinical and laboratory features, bone marrow pathology, and overall disease course.

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Acknowledgments

Our funding was from the following sources: Supported in part by the MD Anderson Cancer Center Support Grant CA016672 and Award Number P01 CA049639.

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Author notes

  1. Prajwal Boddu and Dai Chihara claim equal contribution to this manuscript and share first authorship.

Affiliations

  1. Department of Leukemia, UT MD Anderson Cancer Center, 1515 Holcombe Blvd (Unit 428), Houston, TX, 77030, USA

    Prajwal Boddu, Lucia Masarova, Naveen Pemmaraju & Srdan Verstovsek

  2. Department of Internal Medicine, University of New Mexico, Albuquerque, NM, USA

    Dai Chihara

  3. Department of Hematopathology, UT MD Anderson Cancer Center, Houston, TX, USA

    Keyur P. Patel

Authors
  1. Prajwal Boddu
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  2. Dai Chihara
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  3. Lucia Masarova
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  4. Naveen Pemmaraju
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  5. Keyur P. Patel
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  6. Srdan Verstovsek
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Contributions

PB, LM, NP, and SV designed the study, performed the data collection, and were involved in writing of the manuscript. DC, LM, KP, and NP were involved in writing and revising the manuscript. All authors reviewed and approved the final version of the manuscript.

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Correspondence to Srdan Verstovsek.

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Boddu, P., Chihara, D., Masarova, L. et al. The co-occurrence of driver mutations in chronic myeloproliferative neoplasms. Ann Hematol 97, 2071–2080 (2018). https://doi.org/10.1007/s00277-018-3402-x

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  • DOI: https://doi.org/10.1007/s00277-018-3402-x

Keywords

  • Philadelphia
  • JAK2
  • CALR
  • MPL
  • Myeloproliferative neoplasm
  • Chronic myeloid leukemia