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Haematologica 2019 Volume 104(1):128-137
Acute Lymphoblastic Leukemia
Clinical and molecular characteristics
of MEF2D fusion-positive B-cell precursor acute lymphoblastic leukemia in childhood, including a novel translocation resulting in MEF2D-HNRNPH1 gene fusion
Kentaro Ohki,1 Nobutaka Kiyokawa,1 Yuya Saito,1,2 Shinsuke Hirabayashi,1,3
Kazuhiko Nakabayashi,4 Hitoshi Ichikawa,5 Yukihide Momozawa,6
7 1,8 4 5 Kohji Okamura, Ai Yoshimi, Hiroko Ogata-Kawata, Hiromi Sakamoto,
1 9 3 10 Motohiro Kato, Keitaro Fukushima, Daisuke Hasegawa, Hiroko Fukushima,
Masako Imai,11 Ryosuke Kajiwara,12 Takashi Koike,13 Isao Komori,14
Atsushi Matsui,15 Makiko Mori,16 Koichi Moriwaki,17 Yasushi Noguchi,18 Myoung-ja Park,19 Takahiro Ueda,20 Shohei Yamamoto,21 Koichi Matsuda,22 Teruhiko Yoshida,5 Kenji Matsumoto,23 Kenichiro Hata,4 Michiaki Kubo,6 Yoichi Matsubara,24 Hiroyuki Takahashi,25 Takashi Fukushima,26
Yasuhide Hayashi,27 Katsuyoshi Koh,16 Atsushi Manabe3 and Akira Ohara25 for the Tokyo Children’s Cancer Study Group (TCCSG)
1Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, Setagaya-ku, Tokyo; 2Department of Hematology/Oncology, Tokyo Metropolitan Children’s Medical Center, Fuchu-shi; 3Department of Pediatrics, St. Luke's International Hospital, Chuo-ku, Tokyo; 4Department of Maternal-Fetal Biology, National Research Institute for Child Health and Development, Setagaya-ku, Tokyo; 5Fundamental Innovative Oncology Core, National Cancer Center Research Institute, Chuo-ku, Tokyo;6Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama-shi, Kanagawa; 7Department of Systems BioMedicine, National Research Institute for Child Health and Development, Setagaya-ku, Tokyo; 8Division of Pediatric Hematology and Oncology, Ibaraki Children’s Hospital, Mito-shi; 9Department of Pediatrics, Dokkyo Medical University, Tochigi; 10Department of Pediatrics, University of Tsukuba Hospital, Ibaraki; 11Department of Pediatrics, Japanese Red Cross Musashino Hospital, Tokyo; 12Department of Pediatrics, Yokohama City University Hospital, Kanagawa; 13Department of Pediatrics, Tokai University School of Medicine, Kanagawa; 14Department of Pediatrics, Matsudo City Hospital, Chiba; 15Department of Pediatrics, Japanese Red Cross Maebashi Hospital, Gunma; 16Department of Hematology/Oncology, Saitama Children’s Medical Center; 17Department of Pediatrics, Saitama Medical Center, Saitama Medical University; 18Department of Pediatrics, Japanese Red Cross Narita Hospital, Chiba; 19Department of Hematology/Oncology, Gunma Children’s Medical Center, Shibukawa-shi; 20Department of Pediatrics, Nippon Medical School, Bunkyo-ku, Tokyo; 21Department of Pediatrics, Showa University Fujigaoka Hospital, Yokohama-shi, Kanagawa; 22Laboratory of Clinical Genome Sequencing Department of Computational Biology and Medical Sciences Graduate School of Frontier Sciences, The University of Tokyo, Minato-ku; 23Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Setagaya-ku, Tokyo; 24Director, National Research Institute for Child Health and Development, Setagaya-ku, Tokyo; 25Department of Pediatrics, Toho University Omori Medical Center, Tokyo; 26Department of Child Health, Faculty of Medicine, University of Tsukuba, Ibaraki and 27Institute of Physiology and Medicine, Jobu University, Takasaki-shi, Gunma, Japan
ABSTRACT
Fusion genes involving MEF2D have recently been identified in pre- cursor B-cell acute lymphoblastic leukemia, mutually exclusive of the common risk stratifying genetic abnormalities, although their true incidence and associated clinical characteristics remain unknown. We identified 16 cases of acute lymphoblastic leukemia and 1 of lym- phoma harboring MEF2D fusions, including MEF2D-BCL9 (n=10), MEF2D-HNRNPUL1 (n=6), and one novel MEF2D-HNRNPH1 fusion. The incidence of MEF2D fusions overall was 2.4% among consecutive precursor B-cell acute lymphoblastic leukemia patients enrolled onto a single clinical trial. They frequently showed a cytoplasmic m chain-pos- itive pre-B immunophenotype, and often expressed an aberrant CD5 antigen. Besides up- and down-regulation of HDAC9 and MEF2C, ele- vated GATA3 expression was also a characteristic feature of MEF2D
Correspondence:
oki-kn@ncchd.go.jp
Received: December 11, 2017. Accepted: August 29, 2018. Pre-published: August 31, 2018.
doi:10.3324/haematol.2017.186320
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