Premium
RAS pathway mutation is an added‐value biomarker in pediatric Philadelphia‐negative B‐cell acute lymphoblastic leukemia with IKZF1 deletions
Author(s) -
Huang YingJung,
Liu HsiChe,
Jaing TangHer,
Wu KangHsi,
Wang ShihChung,
Yen HsiuJu,
Hsiao ChihCheng,
Chen ShihHsiang,
Lin PeiChin,
Yeh TingChi,
Sheen JiunnMing,
Chen YuChieh,
Chang TeKau,
Huang FangLiang,
Chao YuHua,
Hou JenYin,
Yang ChaoPing,
Lin TungHuei,
Shih LeeYung
Publication year - 2021
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.28899
Subject(s) - medicine , multiplex ligation dependent probe amplification , oncology , mutation , gene , sanger sequencing , leukemia , biomarker , cancer research , genetics , biology , exon
Background IKZF1 deletion is an unfavorable factor in Philadelphia negative (Ph ‐) B‐cell acute lymphoblastic leukemia. However, the effects of IKZF1 deletions co‐existing genetic alterations in Ph (‐) ALL have not been extensively studied. Methods Bone marrow samples from 368 children with Ph (‐) ALL were analyzed by using multiplex ligation‐dependent probe amplification kit for detection of gene deletions and Sanger sequencing for mutational analysis of RAS pathway genes. The outcome was analyzed on 215 patients treated with Taiwan Pediatric Oncology Group‐ALL‐2002 protocol. Results IKZF1 deletions were present in 12.8% and IKZF1 plus in 6.3% of patients. Mutations of RAS pathway genes were detected in 25.0% of IKZF1 ‐deleted patients. The 10‐year event‐free survival (EFS) of IKZF1 ‐undeleted patients was significantly better compared with IKZF1‐ deleted patients (80.0% vs. 47.8%, p = 0.001). Compared with outcome of patients harboring IKZF1 deletion alone, no difference in EFS was observed in patients with IKZF1 plus , whereas three patients carried both IKZF1 and ERG deletions had a superior 10‐year EFS (100%). The 10‐year EFS of patients with any gene mutation of RAS pathway was worse than that of patients with wild‐type genes (79.1% vs. 61.6%, p = 0.033). In multivariate analysis, RAS pathway mutations and IKZF1 deletion were independent predictors of inferior EFS. Co‐existence of IKZF1 deletion with RAS pathway mutations had a worst 10‐year EFS (11.1 ± 10.5%) and 10‐year OS (53.3 ± 17.6%). Conclusions Our results showed that RAS pathway mutation is an added‐value biomarker in pediatric IKZF1 ‐deleted Ph (‐) ALL patients.