Differential gene expression changes and their implication on the disease progression in patients with Chronic Myeloid Leukemia

Abstract

The molecular mechanisms responsible for disease progression of CML are not conclusive. The main functional changes associated with disease evolution in CML was high proliferation rate, decreased apoptosis, blockade of differentiation, and strong resistance to chemotherapeutic agents. The current study analyzed the relative expressional profiles of genes related with proliferation, apoptosis, differentiation, and resistance to chemotherapeutic agents such as c-MYC, BAD, BCL-2, C/EBPα/-β and ABCB1 respectively in different clinical stages of CML by SYBR Green I quantitative real-time (qRT) PCR. We selected a total of 183 CML patients and 30 healthy control samples. The study populations were classified into four groups, including de novo CML-CP (50/183), CML-AP (32/183), CML-BC (51/183) and Imatinib Mesylate or IM resistant CML-CP (50/183) groups. qRT PCR analysis revealed that significant overexpression of c-MYC, ABCB1 and BCL-2 was observed in advanced phases and IM resistant CP of CML compared to healthy controls. Likewise, the mean expression level of BAD, C/EBPα/-β genes were found to be significantly down regulated. Present study concluded that the complex interplay of several candidate genes like overexpression of c-MYC, ABCB1, BCL-2 and down regulation of BAD, C/EBPα/-β played a significant role in the disease evolution and development of drug resistant in CML.

Keywords: Chronic Myeloid Leukemia; Disease progression; Imatinib Mesylate; Quantitative real time PCR.