Study of PTCH1 Gene as a Prognostic Marker to Predict Imatinib Response on Egyptian CML Patients in Chronic Phase

Abstract

hronic myeloid leukaemia (CML) is a myeloproliferative disorder characterized by a reciprocal translocation between chromosomes 9 and 22 [t (9;22) (q34; q11)], creating the Philadelphia chromosome and bringing together the Breakpoint Cluster Region (BCR) and Abelson (ABL1) genes. The protein encoded by this fusion gene is a dysregulated tyrosine kinase that phosphorylates multiple downstream proteins resulting in changes in cell proliferation, DNA repair, differentiation and cell cycling. The tyrosine kinase inhibitors (TKI), of which imatinib is the most widely used, block BCR-ABL1 tyrosine kinase activity by the competitive inhibition of ATP binding, resulting in a dramatic reduction in the differentiation and proliferation of BCR-ABL1 positive cells.