IKZF1 deletion is associated with a poor outcome in pediatric B‐cell precursor acute lymphoblastic leukemia in Japan

Cancer Medicine

Daisuke Asai¹²  Toshihiko Imamura¹²  So-ichi Suenobu⁴  Akiko Saito⁵  Daiichiro Hasegawa⁸  Takao Deguchi¹  Yoshiko Hashii³  Kimikazu Matsumoto⁹  Hirohide Kawasaki⁶  Hiroki Hori¹  Akihiro Iguchi¹⁰  Yoshiyuki Kosaka⁸  Koji Kato⁹  Keizo Horibe⁵  Keiko Yumura-Yagi^7,12  Junichi Hara^2,12  Megumi Oda^11,12 

[1] Department of Pediatrics, Mie University, Tsu, Japan;Department of Pediatrics, Osaka City General Hospital, Osaka, Japan;Department of Pediatrics, Osaka University, Suita, Japan;Department of Pediatrics, Oita University, Oita, Japan;Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan;Department of Pediatrics Kansai, Medical University, Hirakata, Japan;Department of Pediatrics, Osaka General Medical Center, Osaka, Japan;Department of hematology/oncology, Hyogo Prefectural Children's Hospital, Kobe, Japan;Department of Hematology Oncology, Children's Medical Center, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan;Department of Pediatrics, Hokkaido University, Sapporo, Japan;Department of Pediatrics, Okayama University, Okayama, Japan;Department of Pediatrics, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan

关键词: Acute lymphoblastic leukemia;    CRLF2;    IKZF1 deletion;    pediatric;   

DOI  :  10.1002/cam4.87

来源: Wiley

【 摘 要 】

Abstract

Genetic alterations of Ikaros family zinc finger protein 1 (IKZF1), point mutations in Janus kinase 2 (JAK2), and overexpression of cytokine receptor-like factor 2 (CRLF2) were recently reported to be associated with poor outcomes in pediatric B-cell precursor (BCP)-ALL. Herein, we conducted genetic analyses of IKZF1 deletion, point mutation of JAK2 exon 16, 17, and 21, CRLF2 expression, the presence of P2RY8-CRLF2 fusion and F232C mutation in CRLF2 in 202 pediatric BCP-ALL patients newly diagnosed and registered in Japan Childhood Leukemia Study ALL02 protocol to find out if alterations in these genes are determinants of poor outcome. All patients showed good response to initial prednisolone (PSL) treatment. Ph⁺, infantile, and Down syndrome–associated ALL were excluded. Deletion of IKZF1 occurred in 19/202 patients (9.4%) and CRLF2 overexpression occurred in 16/107 (15.0%), which are similar to previous reports. Patients with IKZF1 deletion had reduced event-free survival (EFS) and overall survival (OS) compared to those in patients without IKZF1 deletion (5-year EFS, 62.7% vs. 88.8%, 5-year OS, 71.8% vs. 90.2%). Our data also showed significantly inferior 5-year EFS (48.6% vs. 84.7%, log rank P = 0.0003) and 5-year OS (62.3% vs. 85.4%, log rank P = 0.009) in NCI-HR patients (n = 97). JAK2 mutations and P2RY8-CRLF2 fusion were rarely detected. IKZF1 deletion was identified as adverse prognostic factor even in pediatric BCP-ALL in NCI-HR showing good response to PSL.

【 授权许可】

CC BY   
© 2013 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

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