Low CREBBP expression is associated with adverse long-term outcomes in paediatric acute lymphoblastic leukaemia.
Eur J Haematol
; 99(2): 150-159, 2017 Aug.
Article
em En
| MEDLINE
| ID: mdl-28452416
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Expressão Gênica
/
Proteína de Ligação a CREB
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Leucemia-Linfoma Linfoblástico de Células Precursoras
Tipo de estudo:
Diagnostic_studies
/
Guideline
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adolescent
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Child
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Child, preschool
/
Female
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Humans
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Infant
/
Male
Idioma:
En
Revista:
Eur J Haematol
Assunto da revista:
HEMATOLOGIA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
China