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.
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.
Authors: Haiying Qin; Monica Cho; Waleed Haso; Ling Zhang; Sarah K Tasian; Htoo Zarni Oo; Gian Luca Negri; Yongshun Lin; Jizhong Zou; Barbara S Mallon; Shannon Maude; David T Teachey; David M Barrett; Rimas J Orentas; Mads Daugaard; Poul H B Sorensen; Stephan A Grupp; Terry J Fry Journal: Blood Date: 2015-06-03 Impact factor: 22.113
Authors: Jason H Rogers; Rohit Gupta; Jaime M Reyes; Michael C Gundry; Geraldo Medrano; Anna Guzman; Rogelio Aguilar; Shannon E Conneely; Tidie Song; Cade Johnson; Sean Barnes; Carlo D D Cristobal; Kristen Kurtz; Lorenzo Brunetti; Margaret A Goodell; Rachel E Rau Journal: Blood Adv Date: 2021-10-12