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Identification of the BRAF V600E mutation in Japanese patients with hairy cell leukemia and related diseases using a quenching probe method

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Abstract

Hairy cell leukemia (HCL) is a rare B-cell lymphoid malignancy that is difficult to distinguish from other morphological variants. The frequency of HCL has not been determined accurately in Japan. Recent studies revealed that the BRAF V600E mutation is the causal genetic event in HCL. We assessed the BRAF mutation in Japanese patients with HCL and related diseases using the quenching probe (QP) method, a single-nucleotide polymorphism detection system, and evaluated the incidence rate of HCL among Japanese patients with chronic lymphocytic leukemia, and related diseases. We identified 18 cases (33.3%) harboring the BRAF mutation among 54 patients diagnosed with, or suspected of having HCL. Of BRAF V600E-positive patients, 7 were only detected using the QP method, not by direct sequencing, whereas 11 were positive using both tests. In a larger cohort of Japanese patients diagnosed with chronic lymphoid leukemia or related diseases, the frequency of HCL was 4%. Patients with the BRAF V600E mutation had a significantly higher frequency of neutropenia, thrombocytopenia, and elevated soluble interleukin-2 receptor and common B-cell surface markers than patients without the mutation. Our results confirm that BRAF V600E-positive HCL is a relatively rare disorder in the Japanese leukemia patient population.

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Acknowledgements

The authors thank all of the patients and all of the investigators at participating institutions.

Author information

Authors and Affiliations

  1. Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan

    Hidekazu Itamura, Naoko Sueoka-Aragane & Shinya Kimura

  2. Department of Internal Medicine, Oda Hospital, Kashima, Japan

    Masaru Ide

  3. Department of Clinical Laboratory Medicine, Faculty of Medicine, Saga University, Saga, Japan

    Akemi Sato & Eisaburo Sueoka

  4. Department of Hematology, Toranomon Hospital, Tokyo, Japan

    Aya Nishida

  5. Department of Hematology, Chugoku Central Hospital, Hiroshima, Japan

    Taro Masunari

  6. Department of Pathophysiology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata, Japan

    Sadao Aoki

  7. Department of Hematology, Endocrinology and Metabolism, Faculty of Medicine, Niigata University, Niigata, Japan

    Jun Takizawa

  8. Department of Oncology/Hematology, School of Medicine, Shimane University, Izumo, Japan

    Junji Suzumiya

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  1. Hidekazu Itamura
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Correspondence to Shinya Kimura.

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Appendices

Appendices

Additional investigators that participated in this study include Drs H. Kuroda (Steel Memorial Muroran Hospital), H. Harigae (Tohoku University Hospital), K. Ishizawa (Yamagata University Hospital), E. Omoto (Yamagata Prefectural Central Hospital), M. Ohnishi (Niigata Minami Hospital), N. Tsukamoto (Gunma University Hospital), K. Murata (Soka City Hospital), K. Kimura (Chiba University Hospital), S. Taniguchi (Toranomon Hospital), K. Kitazume (Showa General Hospital), K. Usuki (NTT Medical Center Tokyo), J. Ando (Juntendo University Hospital), K. Miura (Nihon University Itabashi Hospital), I. Miura (St. Marianna University Hospital), R. Sakai (Kanagawa Cancer Center Hospital), K. Matsumoto (Yokohama City University Hospital), C. Hashimoto (Yamato Municipal Hospital), M. Koike (Juntendo University Shizuoka Hospital), H. Kobayashi (Nagano Red Cross Hospital), F. Ishida (Shinshu University Hospital), J. Murakami (Toyama University Hospital), S. Matano (Tonami General Hospital), Y. Masaki (Kanazawa Medical University Hospital), C. Sugimori (Ishikawa Prefectural Central Hospital), T. Yamashita (Keiju Medical Center), K. Yamamoto (Aichi Cancer Center), Y. Miyata (Nagoya Medical Center), T. Uchida (Nagoya Red Cross Daini Hospital), S. Kasahara (Gifu City Hospital), A. Takaori (Kyoto University Hospital), M. Hino (Osaka City University Hospital), H. Mitsui (Otemae Hospital), M. Nogawa (Japanese Red Cross Wakayama Medical Center), E. Kondo (Okayama University Hospital), T. Okada (Kurashiki central Hospital), M. Uno (Kaneda Hospital), T. Kiguchi (Chugoku Central Hospital), H. Asaoku (Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital), R. Nawata (JCHO Shimonoseki Medical Center), T. Shibuya (Shin-Kokura Hospital), Y. Takamatsu (Fukuoka University Hospital), Y. Suehiro (National Hospital Organization Kyushu Cancer Center), Y. Imaizumi (Nagasaki University Hospital), E. Ohtsuka (Oita Prefectural Hospital), T. Ando (Tsurumi Hospital), H. Yamasaki (Kumamoto City Hospital), A. Utsunomiya (Imamura Bun-in Hospital), and K. Miyagi (Heartlife Hospital).

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Itamura, H., Ide, M., Sato, A. et al. Identification of the BRAF V600E mutation in Japanese patients with hairy cell leukemia and related diseases using a quenching probe method. Int J Hematol 108, 416–422 (2018). https://doi.org/10.1007/s12185-018-2506-3

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