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Acute Leukemias

Involvement of mast cells by the malignant process in patients with Philadelphia chromosome negative myeloproliferative neoplasms

Leukemia volume 23, pages 1577–1586 (2009)Cite this article

Abstract

The Philadelphia chromosome negative myeloproliferative neoplasms (MPNs) are clonal hematologic malignancies frequently characterized by a mutation in JAK2 (JAK2V617F). Peripheral blood (PB) CD34+ cells from patients with polycythemia vera (PV) and primary myelofibrosis (PMF) generated in vitro significantly fewer mast cells (MCs) than normal PB CD34+ cells. The numbers of MC progenitors assayed from MPN CD34+ cells were, however, similar to that assayed from normal CD34+ cells. A higher percentage of the cultured MPN MCs expressed FcɛRIα, CD63 and CD69 than normal MCs, suggesting that cultured MPN MCs are associated with an increased state of MC activation. Further analysis showed that a higher proportion of cultured PV and PMF MCs underwent apoptosis in vitro. By using JAK2V617F, MplW515L and chromosomal abnormalities as clonality markers, we showed that the malignant process involved MPN MCs. JAK2V617F-positive MC colonies were assayable from the PB CD34+ cells of each of the 17 JAK2V617F positive MPN patients studied. Furthermore, erlotinib, a JAK2 inhibitor, was able to inhibit JAK2V617F-positive PV MC progenitor cells, indicating that malignant MC progenitor cells are a potential cellular target for such JAK2 inhibitor-directed therapy.

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Acknowledgements

We thank Mrs Amy Rodriguez for helping us to obtain patient specimens. Erlotinib was a gift from OSI Pharmaceuticals. This study was supported by grants from the Department of Defense (MP048007 to MX) and Leukemia and Lymphoma Society of America (to MX). JW and TI performed most of the experiments and contributed equally to this work. VN performed and analyzed the FISH studies. JM, RH and NW acquired the patient specimens. TI analyzed the data and drafted the manuscript. WZ and YD assisted the experiments. ZZ provided assistance in designing the study. SS and JW performed the laser capture microdissection. MX designed and supervised the studies, wrote the manuscript and responsible for its final draft.

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Authors and Affiliations

  1. Division of Hematology/Oncology, Department of Medicine, Tisch Cancer Institute, New York, NY, USA

    J Wang, T Ishii, W Zhang, S Sozer, Y Dai, J Mascarenhas, V Najfeld, R Hoffman, N Wisch & M Xu

  2. Edmond H. Fischer Signal Transduction Laboratory, College of Life Science, Jilin University, Changchun, China

    J Wang & Z J Zhao

  3. Department of Pathology, Mount Sinai School of Medicine, New York, NY, USA

    V Najfeld

  4. The Myeloproliferative Disorder Research Consortium, New York, NY, USA

    V Najfeld, R Hoffman & M Xu

  5. Department of Pathology, University of Oklahoma Health Science Center, Oklahoma City, OK, USA

    Z J Zhao

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  1. J Wang
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Correspondence to M Xu.

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Wang, J., Ishii, T., Zhang, W. et al. Involvement of mast cells by the malignant process in patients with Philadelphia chromosome negative myeloproliferative neoplasms. Leukemia 23, 1577–1586 (2009). https://doi.org/10.1038/leu.2009.85

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