Chronic Myeloid Leukemia (CML) is a myeloproliferative neoplasm of the hematopoietic system, characterized by the presence of the BCR-ABL oncoprotein due to the chromosomal translocation t (9;22). This oncoprotein has elevated tyrosine kinase activity, which leads to enhanced proliferation, reduced differentiation and apoptosis, increased angiogenesis etc. Even though several targeted tyrosine kinase inhibitors (TKIs) such as imatinib, dasatinib etc. are being employed in treating CML, a proportion of patients (25-30%) exhibit resistance to TKIs leading to treatment failure and unchecked disease progression. Progression of CML may be due to genetic instability which include chromosomal translocations, mutations, polymorphisms and gene amplification which ultimately causes up and down regulation of genes in various pathways including angiogenesis. Increased angiogenesis is associated with CML due to the up regulation of various angiogenic factors and their transcriptional regulators, which in turn has been found to lead to disease progression to advanced phases, as the protein products of these genes may act synergistically with BCR-ABL oncoprotein in advancing the disease. Single nucleotide polymorphisms (SNPs) are one of the causes for up regulation of antigenic genes and are associated with susceptibility and progression of CML by affecting therapeutic outcome. This review focuses mainly on the role of upregulated pro-angiogenic factors- VEGF, IL-8 and their transcriptional regulators HIF1α, NF-kB and also the role of SNPs in these genes in disease susceptibility, progression, drug response, prognosis and survival in CML patients. Identification of SNPs and up regulated genes of angiogenesis may serve as biomarkers for predicting disease progression, drug response, prognosis etc. Anti-angiogenic therapy is aimed at targeting the new blood vessels that supply nutrients to rapidly growing tumor cells. Combinations of targeted therapy and anti-angiogenic therapy may serve as the novel therapeutic strategies in overcoming drug resistance and thereby preventing the disease progression in CML.
