RAS pathway mutation is an added-value biomarker in pediatric Philadelphia-negative B-cell acute lymphoblastic leukemia with IKZF1 deletions

doi:10.1002/pbc.28899

中山醫學大學機構典藏 CSMUIR > 中山醫學大學研究成果 > 期刊論文 > Item 310902500/23515

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/23515

Title:	RAS pathway mutation is an added-value biomarker in pediatric Philadelphia-negative B-cell acute lymphoblastic leukemia with IKZF1 deletions
Authors:	Huang, YJ;Liu, HC;Jaing, TH;Wu, KH;Wang, SC;Yen, HJ;Hsiao, CC;Chen, SH;Lin, PC;Yeh, TC;Sheen, JM;Chen, YC;Chang, TK;Huang, FL;Chao, YH;Hou, JY;Yang, CP;Lin, TH;Shih, LY
Keywords:	IKZF1 deletion;pediatric;Philadelphia-negative B-ALL;RAS pathway gene mutation
Date:	2021
Issue Date:	2022-08-05T09:38:31Z (UTC)
Publisher:	WILEY
ISSN:	1545-5009
Abstract:	Background: IKZF1deletion 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.
URI:	http://dx.doi.org/10.1002/pbc.28899 https://www.webofscience.com/wos/woscc/full-record/WOS:000613406600001 https://ir.csmu.edu.tw:8080/handle/310902500/23515
Relation:	PEDIATRIC BLOOD & CANCER ,2021,v68,issue 4
Appears in Collections:	[中山醫學大學研究成果] 期刊論文

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