Association of HOXA4 Gene Expression and Methylation with Response to Treatment in Iraqi Chronic Myeloid Leukemia Patients

Abstract

Genetic and epigenetic factors affect Chronic Myeloid Leukemia (CML) response to Imatinib mesylate (IM) therapy. This study aimed to investigate HOXA4 gene methylation and expression in CML patients and their predictive value as response markers. Blood samples were collected from fifty CML patients (25 responders and 25 non-responders to Imatinib mesylate therapy) and 50 healthy controls of same age and sex. HOXA4 gene methylation and gene expression studies were conducted by quantitative PCR (qPCR). Results revealed that CML patients had significantly higher level of HOXA4 gene demethylation and expression compared to controls group (p <0.001). The non-responders CML patients showed higher significant levels of HOXA4 gene demethylation (p<0.001) and expression (p<0.05) compared to responders CML patients. Significant risk association results of HOXA4 demethylation and expression levels (p<0.001 and p<0.05, respectively) with the development of IM resistance in CML patients according to optimal cut-off point obtained by receiver operating characteristics (ROC) analysis. In conclusion, HOXA4 gene activation due to promoter DNA hypomethylation refers to its oncogenic role in CML pathogenesis. HOXA4 gene demethylation and overexpression may serve as biomarkers for predicting IM resistance in CML patients, especially HOXA4 gene demethylation with good sensitivity and specificity.