Chao Gao1,2,3,4,5, Rui-Dong Zhang2,3,4,5, Shu-Guang Liu2,3,4,5, Xiao-Xi Zhao2,3,4,5, Lei Cui2,3,4,5, Zhi-Xia Yue2,3,4,5, Wei-Jing Li2,3,4,5, Zhen-Ping Chen2,3,4,5, Zhi-Gang Li2,3,4,5, Qing Rao1, Min Wang1, Hu-Yong Zheng2,3,4,5, Jian-Xiang Wang1. 1. Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China. 2. Beijing Key Laboratory of Pediatric Hematology Oncology, Beijing, China. 3. Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing, China. 4. National Key Discipline of Pediatrics, Ministry of Education, Beijing, China. 5. Hematology and Oncology Center, Beijing Children's Hospital, Capital Medical University, Beijing, China.
Abstract
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.
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-CREBBPpatients 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 insufficientCREBBP and that a specific target therapy is necessitated for high-risk patients.