Recurrent 8q24 rearrangement in blastic plasmacytoid dendritic cell neoplasm: association with immunoblastoid cytomorphology, MYC expression, and drug response

Kana Sakamoto, Ryohei Katayama, Reimi Asaka, Seiji Sakata, Satoko Baba, Hideki Nakasone, Sumie Koike, Naoko Tsuyama, Akito Dobashi, Makoto Sasaki, Ryo Ichinohasama, Emi Takakuwa, Rie Yamazaki, Jun Takizawa, Takahiro Maeda, Miwako Narita, Koji Izutsu, Yoshinobu Kanda, Koichi Ohshima, Kengo Takeuchi

研究成果: Article査読

29 被引用数 (Scopus)

抄録

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare skin-tropic hematological malignancy of uncertain pathogenesis and poor prognosis. We examined 118 BPDCN cases for cytomorphology, MYC locus rearrangement, and MYC expression. Sixty-two (53%) and 41 (35%) cases showed the classic and immunoblastoid cytomorphology, respectively. Forty-one (38%) MYC+BPDCN (positive for rearrangement and expression) and 59 (54%) MYCBPDCN (both negative) cases were identified. Immunoblastoid cytomorphology was significantly associated with MYC+BPDCN. All examined MYC+BPDCNs were negative for MYB/MYBL1 rearrangement (0/36). Clinically, MYC+BPDCN showed older onset, poorer outcome, and localized skin tumors more commonly than MYCBPDCN. MYC was demonstrated by expression profiling as one of the clearest discriminators between CAL-1 (MYC+BPDCN) and PMDC05 (MYCBPDCN) cell lines, and its shRNA knockdown suppressed CAL-1 viability. Inhibitors for bromodomain and extra-terminal protein (BETis), and aurora kinases (AKis) inhibited CAL-1 growth more effectively than PMDC05. We further showed that a BCL2 inhibitor was effective in both CAL-1 and PMDC05, indicating that this inhibitor can be used to treat MYCBPDCN, to which BETis and AKis are probably less effective. Our data will provide a rationale for the development of new treatment strategies for patients with BPDCN, in accordance with precision medicine.

本文言語English
ページ(範囲)2590-2603
ページ数14
ジャーナルLeukemia
32
12
DOI
出版ステータスPublished - 2018 12 1

ASJC Scopus subject areas

  • 血液学
  • 腫瘍学
  • 癌研究

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