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IKZF 1 and CRLF 2 gene alterations correlate with poor prognosis in Japanese BCR ‐ ABL 1 ‐negative high‐risk B‐cell precursor acute lymphoblastic leukemia
Author(s) -
Yamashita Yuka,
Shimada Akira,
Yamada Tomomi,
Yamaji Kazutaka,
Hori Toshinori,
Tsurusawa Masahito,
Watanabe Arata,
Kikuta Atsushi,
Asami Keiko,
Saito Akiko M.,
Horibe Keizo
Publication year - 2013
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.24571
Subject(s) - medicine , oncology , cancer , clinical significance , lymphoblastic leukemia , gene , gastroenterology , leukemia , genetics , biology
Background Genome‐wide analysis studies have demonstrated that IKZF1 , CRLF2 , and JAK2 gene alterations correlate with poor prognosis in pediatric B‐cell precursor acute lymphoblastic leukemia (BCP‐ALL). However, the prognostic significance for these gene alterations has not been clarified in Japanese patients. Procedure A total of 194 patients with BCP‐ALL enrolled in the Japanese Children's Cancer & Leukemia Study Group ALL 2004 clinical trial were assessed for the presence of three different gene alterations: IKZF1 deletions, CRLF2 expression and JAK2 mutation. Results IKZF1 deletions and CRLF2 ‐high expression were identified in 22 of 177 (12%) patients and in 15 of 141 (11%) patients, respectively. However, JAK2 R683 mutation was detected only one of 177 patients. The 4‐year event‐free survival (4y‐EFS) was different when comparing patients with or without IKZF1 deletions (68.2% vs. 85.2%; P = 0.04) and was also different when comparing patients with different CRLF2 expression levels (high, 66.7% vs. low, 88.1%; P = 0.03). The differences in 4y‐EFS were statistically significant in patients with ALL in the National Cancer Institute (NCI)‐high risk group (HR‐ALL) ( IKZF1 deletions: yes, 58.3% vs. no, 87.0%, P = 0.02; CRLF2 expression: high, 55.6% vs. low, 85.3%, P = 0.04) but not in patients with ALL in the NCI‐standard risk group (SR‐ALL; IKZF1 deletions: yes, 80.0% vs. no, 84.4%, P = 0.75; CRLF2 expression: high, 83.3% vs. low, 89.2%, P = 0.77). Coexistence of IKZF1 deletions and CRLF2 ‐high expression associated with poor outcomes. Conclusions IKZF1 deletions and CRLF2 ‐high expression predicted poor outcomes in patients with HR‐ALL but not in patients with SR‐ALL in our Japanese cohort. Pediatr Blood Cancer 2013;60:1587–1592. © 2013 Wiley Periodicals, Inc.