Low CREBBP expression is associated with adverse long‐term outcomes in paediatric acute lymphoblastic leukaemia

• Published in: European journal of haematology 2017-08, Vol.99 (2), p.150-159
• Main Authors: Gao, Chao, Zhang, Rui‐Dong, Liu, Shu‐Guang, Zhao, Xiao‐Xi, Cui, Lei, Yue, Zhi‐Xia, Li, Wei‐Jing, Chen, Zhen‐Ping, Li, Zhi‐Gang, Rao, Qing, Wang, Min, Zheng, Hu‐Yong, Wang, Jian‐Xiang
• Format: Article
• Language: English
• Subjects: acute lymphoblastic leukaemia; Acute lymphoblastic leukemia; Adolescent; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Child; Child, Preschool; clinical studies; CREB-Binding Protein - genetics; CREBBP; Cytogenetic Analysis; DNA Mutational Analysis; Female; Gene Expression; Humans; Immunophenotyping; Infant; Kaplan-Meier Estimate; Leukemia; Male; Minimal residual disease; Mutation; paediatrics; Precursor Cell Lymphoblastic Leukemia-Lymphoma - diagnosis; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics; Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality; Precursor Cell Lymphoblastic Leukemia-Lymphoma - therapy; Prednisone; Prognosis; Remission; Remission Induction; Risk groups; Survival; Treatment Outcome
• ISSN: 0902-4441; 1600-0609
• DOI: 10.1111/ejh.12897

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 (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.