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JAK2V617F mutation status and allele burden in classical Ph-negative myeloproliferative neoplasms in Japan

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Abstract

JAK2V617F, a gain-of-function mutation in the tyrosine kinase JAK2, is frequently detected in classical myeloproliferative neoplasms (MPNs). In the present study, we determined the JAK2V617F allele burden in Japanese MPN patients using alternately binding probe competitive-polymerase chain reaction, a highly quantitative method recently developed by our group. Although we observed strong similarities in terms of epidemiological parameters associated with the JAK2V617F allele burden between our cohort and others, we found a higher JAK2V617F allele burden in Japanese polycythemia vera (PV) patients and lower frequencies of thrombosis in Japanese MPN patients compared with previous reports. In addition, despite the presence of high red blood cell counts, some patients bearing the JAK2V617F mutation were not diagnosed as PV, as their hemoglobin values were lower than the WHO PV criterion. In these patients, the JAK2V617F allele burden was strikingly similar to that in PV patients fulfilling the 2008 WHO criteria, suggesting that these patients can be classified as PV. Although isotopic measurement of red cell mass (RCM) is required for definitive diagnosis of PV, our data suggest that precise measurement of the JAK2V617F allele burden may improve the diagnosis of PV when RCM has not been determined.

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Acknowledgments

We thank Kazuhiko Ikeda (Fukushima Medical University), Nobuyoshi Hanaoka (Wakayama Medical University), Toshiro Kurokawa (Toyama Red Cross Hospital), Hideo Harigae (Tohoku University), Takayuki Ikezoe (Kochi University), Jun Murakami (University of Toyama), Kensuke Usuki (NTT Kanto Medical Center), and Takao Hirano (Juntendo Nerima Hospital) for providing patient specimens and clinical information. We also thank Masaki Kobayashi and Ei Leen Liew for technical assistance and fruitful discussions; Yuki Kagawa for advice on statistics; Kyoko Kubo, Kazuko Kawamura, and Megumi Hasegawa for secretarial assistance; and other members of the Department of Hematology for support in this study. We also acknowledge the Laboratory of Molecular and Biochemical Research, Research Support Center, Juntendo University Graduate School of Medicine. This work was funded in part by JSPS (http://www.jsps.go.jp/english/e-grants/) KAKENHI Grant #25860416 (SM). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Conflict of interest

The authors declare no competing interests.

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Authors and Affiliations

  1. Department of Hematology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan

    Yoko Edahiro, Kochi Takahashi, Yumi Hironaka, Yuriko Yahata, Yoshitaka Sunami, Shuichi Shirane, Miyuki Tsutsui & Norio Komatsu

  2. Department of Transfusion Medicine and Stem Cell Regulation, Juntendo University Graduate School of Medicine, Tokyo, Japan

    Soji Morishita, Akimichi Ohsaka & Marito Araki

  3. Department of Life Science and Medical Bioscience, Waseda University, Tokyo, Japan

    Kochi Takahashi & Satoshi Tsuneda

  4. Department of Hematology, Juntendo Urayasu Hospital, Chiba, Japan

    Masaaki Noguchi

  5. Department of Hematology, Juntendo Shizuoka Hospital, Shizuoka, Japan

    Michiaki Koike

  6. Department of Hematology, Sapporo Hokuyu Hospital, Hokkaido, Japan

    Kiyotoshi Imai

  7. Department of Hematology and Oncology, Yamanashi University, Yamanashi, Japan

    Keita Kirito

  8. Bio-Measurement Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Ibaraki, Japan

    Naohiro Noda & Yuji Sekiguchi

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  1. Yoko Edahiro
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Correspondence to Norio Komatsu.

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Edahiro, Y., Morishita, S., Takahashi, K. et al. JAK2V617F mutation status and allele burden in classical Ph-negative myeloproliferative neoplasms in Japan. Int J Hematol 99, 625–634 (2014). https://doi.org/10.1007/s12185-014-1567-1

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  • DOI: https://doi.org/10.1007/s12185-014-1567-1

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