Relationship between Class I HDACs Gene Expression and Multidrug Resistance Genes in Childhood Acute Lymphoblastic Leukemia

BM13

Moreno, Daniel Antunes (1) (danielmoreno@usp.br); Cortez, Maria Angélica Abdála (1); Yunes, José Andres (2); Brandalise, Sílvia Regina (2); Scrideli, Carlos Alberto (3); Tone, Luiz Gonzaga (3).

(1) Departamento de Genética da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (FMRP-USP)

(2) Universidade Estadual de Campinas

(3) Departamento de Puericultura e Pediatria da FMRP-USP

Introduction. One of the most important causes of failure in the treatment of acute lymphoblastic leukemia (ALL) is celular multidrug resistance (MDR). The altered expression of genes related with MDR as MDR1, MRP1, MRP3, BCRP and LRP, is a common feature observed in cancer and recently, some studies have shown that epigenetic drugs known as histone deacetylase inhibitors (HDACi) promote apoptosis in drug-resistant leukemia cells although the molecular mechanisms involved in this process remain unclear. Histone deacetylase (HDACs) enzymes, which are associated with chromatin condensation and transcriptional repression, virtually can control trasncriptional activity of many genes including MDR genes. Objectives. To investigate the relationship between gene expression of class I HDACs (HDAC1, HDAC2, HDAC3 and HDAC8) and multidrug resistance genes (MDR1, MRP1, MRP3, BCRP and LRP) in ALL. Methods. Expression of class I HDACs and MDR genes were analyzed in 89 consecutive bone marrow samples obtained from pediatric patients with ALL using real-time polymerase chain reaction. The Spearman correlation test was the statistical method utilized. Results. We observed a negative correlation between HDAC3 and MRP1 (p=-0,002); HDAC8 and MRP1 (p=-0,039); HDAC8 and BCRP (p=-0,094). It was observed correlation in gene expression of HDAC1, HDAC2, HDAC3 and HDAC8. MDR genes also showed correlation, except BCRP that was associated only with MRP1 (p=0,007). We also found correlation between HDAC3 and MDR1 (p=0,042); HDAC3 and MRP3 (p=0,046); HDAC2 and MRP3 (p=0,047). Conclusion. These results suggest that class I HDACs gene expression can be related with MDR genes and this association is important for understanding the molecular mechanisms involved in MDR in childhood ALL, however it is necessary to perform functional investigation to confirm these results.