mRNA Expression Profile of Multidrug Resistance Genes in Childhood Acute Lymphoblastic Leukemia. Low Expression Levels Associated With a Higher Risk of Toxic Death

Autor(es)

Cortez, Maria A. A. ^[1] ; Scrideli, Carlos A. ^[2] ; Yunes, Jose A. ^[3] ; Valera, Elvis T. ^[2] ; Toledo, Silvia R. C. ^[4] ; Pavoni-Ferreira, Patricia C. B. ^[4] ; Lee, Maria L. M. ^[4] ; Petrilli, Antonio S. ^[4] ; Brandalise, Silvia R. ^{[3, 5]} ; Tone, Luiz G. ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Genet, BR-14048900 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Pediat, BR-14048900 Ribeirao Preto, SP - Brazil

^[3] Ctr Infantil Boldrini, Sao Paulo - Brazil

^[4] Univ Fed Sao Paulo, Inst Pediat Oncol, Sao Paulo - Brazil

^[5] Univ Estadual Campinas, Dept Pediat, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PEDIATRIC BLOOD & CANCER; v. 53, n. 6, p. 996-1004, DEC 1 2009.
• Citações Web of Science: 28

Resumo

Background. Increased activity of multidrug resistance (MDR) genes has been associated with treatment failure in acute leukemias, although with controversial reports. The objective of the present study was to assess the expression profile of the genes related to MDR: ABCB1, ABCC1, ABCC3, ABCC2, and LRP/MVP in terms of the clinical and biological variable and the survival of children with acute lymphoblastic leukemia (ALL). Procedure. The levels of mRNA expression of the drug resistance genes ABCB1, ABCC1, ABCC3, ABCG2, and LRP/MVP were analyzed by quantitative real-time PCR using the median Values as cut-off points, in consecutive samples from 140 children with ALL at diagnosis. Results. Expression levels of the ABCG2 gene in the patient group as a whole (P=0.05) and of the ABCG2 and ABCC1 genes in patients classified as being at high risk were associated with higher rates of 5-year event-free survival (EFS) (P=0.04 and P=0.01). Expression levels of the ABCG2 gene below the median were associated with a greater chance of death related to treatment toxicity for the patient group as a whole (P=0.009) and expression levels below the median of the ABCG2 and ABCC1 genes were associated with a greater chance of death due to treatment toxicity for the high-risk group (P=0.02 and P=0.03, respectively). Conclusion. The present data suggest a low participation of the drug efflux genes in treatment failure in patients with childhood ALL. However, the low expression of some of these genes may be associated with a higher death risk related to treatment toxicity. Pediatr Blood Cancer 2009;53:996-1004. (C) 2009 Wiley-Liss, Inc. (AU)

• Processo FAPESP: 02/03182-8 - Genoma clínico: avaliação dos grupos filiados
• Beneficiário: Silvia Regina Brandalise
• Modalidade de apoio: Auxílio à Pesquisa - Programa GENOMA
• Processo FAPESP: 05/50731-5 - Estudo do padrão da expressão de genes relacionados à resistência/sensibilidade aos quimioterápicos na leucemia linfóide aguda da criança e do adolescente
• Beneficiário: Luiz Gonzaga Tone
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 01/13206-9 - Padrão da expressão gênica da leucemia linfoblástica aguda da infância associada à resistência à quimioterapia
• Beneficiário: Luiz Gonzaga Tone
• Modalidade de apoio: Auxílio à Pesquisa - Programa GENOMA