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ASXL1 alteration cooperates with JAK2V617F to accelerate myelofibrosis

Leukemia volume 33, pages 1287–1291 (2019)Cite this article

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To the Editor:

M yeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders. MPNs are characterized by aberrant hematopoietic proliferation of one or more hematopoietic cell lineages with increased risks of myelofibrosis (MF) progression and leukemic transformation [1]. MPNs are distinguished into three clinical entities: polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) [2]. The somatic mutation of JAK2V617F is considered to be the most notable landmark in the diagnosis of classic Philadelphia chromosome-negative MPNs and is present in >95% of PV patients and in ~50% of ET and PMF [3, 4]. High-throughput genomic analyses of MPN patients have identified the concurrent somatic mutations of epigenetic regulators such as ASXL1, TET2, IDH, EZH2, and DNMT3A co-occurring with JAK2 mutation, which are involved in clonal evolution, disease progression, and/or poor survival in MPNs [5, 6]. ASXL1 (additional sex combs-like 1) is a polycomb group protein that putatively functions as a chromatin modifier. ASXL1 mutations were identified in all types of myeloid malignancies [7,8,9,10,11]. In all, 34.5% of ASXL1 mutations are found in PMF patients [11]. Despite the significant impact of ASXL1 alteration and JAK2V617F on the pathogenesis of MPNs, the importance of concomitant alterations of ASXL1 and JAK2V617F within distinct hematopoietic compartments and disease progression remains to be elucidated.

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Acknowledgements

This work was supported by grants from the NIH (CA172408 to F-CY and MX), the Leukemia & Lymphoma Society (Specialized Center of Research grant to F-CY, MX, and SDN), and National Natural Science Foundation of China (81770128 to YZ).

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  1. These authors contributed equally: Ying Guo, Yuan Zhou

Authors and Affiliations

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

    Ying Guo, Shohei Yamatomo, Hui Yang, Peng Zhang, Shi Chen, Stephen D. Nimer, Mingjiang Xu & Feng-Chun Yang

  2. Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL, USA

    Ying Guo, Shohei Yamatomo, Hui Yang, Peng Zhang, Shi Chen, Stephen D. Nimer, Mingjiang Xu & Feng-Chun Yang

  3. State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China

    Yuan Zhou & Jie Bai

  4. Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA

    Zhizhuang Joe Zhao

  5. Department of Hematology, the Second Hospital of Tianjin Medical University, Tianjin, China

    Jie Bai

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Guo, Y., Zhou, Y., Yamatomo, S. et al. ASXL1 alteration cooperates with JAK2V617F to accelerate myelofibrosis. Leukemia 33, 1287–1291 (2019). https://doi.org/10.1038/s41375-018-0347-y

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