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Low CREBBP expression is associated with adverse long‐term outcomes in paediatric acute lymphoblastic leukaemia
Author(s) -
Gao Chao,
Zhang RuiDong,
Liu ShuGuang,
Zhao XiaoXi,
Cui Lei,
Yue ZhiXia,
Li WeiJing,
Chen ZhenPing,
Li ZhiGang,
Rao Qing,
Wang Min,
Zheng HuYong,
Wang JianXiang
Publication year - 2017
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/ejh.12897
Subject(s) - medicine , oncology
Objectives CREBBP alterations are associated with many diseases including leukaemia. However, CREBBP expression and its clinical relevance in paediatric acute lymphoblastic leukaemia have not been elucidated. Methods We studied CREBBP mRNA expression in 349 patients treated with either the BCH‐2003 or CCLG‐2008 protocol. Using a receiver operating characteristic curve, patients were divided into low‐ or high‐ CREBBP . The association among clinicobiological characteristics, outcomes and CREBBP level was analysed. Results Low expression of CREBBP (<1.0) at diagnosis was found in 97.7% of patients and increased significantly after complete remission. Low‐ CREBBP patients were associated with unfavourable clinical presentations, poor prednisone response and high minimal residual disease (>10 −2 ) after induction. We found significantly poorer event‐free survival (EFS) and overall survival (OS) in low‐ CREBBP group whether administered BCH‐2003 or CCLG‐2008. Low‐ CREBBP was an inferior independent prognostic factor in BCH‐2003; patients with low‐ CREBBP had better outcomes on an intermediate‐risk regimen than a standard‐risk regimen involving the CCLG‐2008 protocol. Patients stratified to high‐risk with low‐ CREBBP had the worst EFS and OS. Conclusions These findings indicate that low‐ CREBBP is predictive of unfavourable outcomes; thus, a more intensive treatment protocol is necessitated for standard‐risk patients with insufficient CREBBP and that a specific target therapy is necessitated for high‐risk patients.