@article{Kentaro Ohki_Nobutaka Kiyokawa_Yuya Saito_Shinsuke Hirabayashi_Kazuhiko Nakabayashi_Hitoshi Ichikawa_Yukihide Momozawa_Kohji Okamura_Ai Yoshimi_Hiroko Ogata-Kawata_Hiromi Sakamoto_Motohiro Kato_Keitaro Fukushima_Daisuke Hasegawa_Hiroko Fukushima_Masako Imai_Ryosuke Kajiwara_Takashi Koike_Isao Komori_Atsushi Matsui_Makiko Mori_Koichi Moriwaki_Yasushi Noguchi_Myoung-ja Park_Takahiro Ueda_Shohei Yamamoto_Koichi Matsuda_Teruhiko Yoshida_Kenji Matsumoto_Kenichiro Hata_Michiaki Kubo_Yoichi Matsubara_Hiroyuki Takahashi_Takashi Fukushima_Yasuhide Hayashi_Katsuyoshi Koh_Atsushi Manabe_Akira Ohara_for the Tokyo Children’s Cancer Study Group (TCCSG)_2018, place={Pavia, Italy}, title={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}, volume={104}, url={https://haematologica.org/article/view/8729}, DOI={10.3324/haematol.2017.186320}, abstractNote={Fusion genes involving <em>MEF2D</em> have recently been identified in precursor 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 lymphoma harboring <em>MEF2D</em> fusions, including <em>MEF2D-BCL9</em> (n=10), <em>MEF2D-HNRNPUL1</em> (n=6), and one novel <em>MEF2D-HNRNPH1</em> fusion. The incidence of <em>MEF2D</em> 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 μ chain-positive pre-B immunophenotype, and often expressed an aberrant CD5 antigen. Besides up- and down-regulation of <em>HDAC9</em> and <em>MEF2C</em>, elevated <em>GATA3</em> expression was also a characteristic feature of <em>MEF2D</em> fusion-positive patients. Mutations of <em>PHF6</em>, recurrent in T-cell acute lymphoblastic leukemia, also showed an unexpectedly high frequency (50%) in these patients. <em>MEF2D</em> fusion-positive patients were older (median age 9 years) with elevated WBC counts (median: 27,300/ml) at presentation and, as a result, were mostly classified as NCI high risk. Although they responded well to steroid treatment, <em>MEF2D</em> fusion-positive patients showed a significantly worse outcome, with 53.3% relapse and subsequent death. Stem cell transplantation was ineffective as salvage therapy. Interestingly, relapse was frequently associated with the presence of <em>CDKN2A/CDKN2B</em> gene deletions. Our observations indicate that <em>MEF2D</em&gt; fusions comprise a distinct subgroup of precursor B-cell acute lymphoblastic leukemia with a characteristic immunophenotype and gene expression signature, associated with distinct clinical features.}, number={1}, journal={Haematologica}, author={Kentaro Ohki and Nobutaka Kiyokawa and Yuya Saito and Shinsuke Hirabayashi and Kazuhiko Nakabayashi and Hitoshi Ichikawa and Yukihide Momozawa and Kohji Okamura and Ai Yoshimi and Hiroko Ogata-Kawata and Hiromi Sakamoto and Motohiro Kato and Keitaro Fukushima and Daisuke Hasegawa and Hiroko Fukushima and Masako Imai and Ryosuke Kajiwara and Takashi Koike and Isao Komori and Atsushi Matsui and Makiko Mori and Koichi Moriwaki and Yasushi Noguchi and Myoung-ja Park and Takahiro Ueda and Shohei Yamamoto and Koichi Matsuda and Teruhiko Yoshida and Kenji Matsumoto and Kenichiro Hata and Michiaki Kubo and Yoichi Matsubara and Hiroyuki Takahashi and Takashi Fukushima and Yasuhide Hayashi and Katsuyoshi Koh and Atsushi Manabe and Akira Ohara and for the Tokyo Children’s Cancer Study Group (TCCSG)}, year={2018}, month={Dec.}, pages={128-137} }