Chronic myelogenous leukemia (CML) is characterized by excessive proliferation of myeloid lineage of cells. The abnormality is caused due to constitutive tyrosine kinase activity of fusion protein Bcr-Abl, resulting from reciprocal chromosomal translocations of ABL from chromosome 9 to BCR on chromosome 22 [1]. The normal cellular Abl (c-Abl) is a multi-domain protein that belongs to non-receptor tyrosine kinase family. It phosphorylates proteins at tyrosine residues. Phosphorylation activity of Abl kinase is under allosteric regulation by its SH2 domain [2,3]. Abl influences several protein-protein interactions and enzymatic activity and localization. C-Abl associates a variety of sub cellular proteins including signaling adaptors, kinases, phosphatases, cell cycle regulators, transcription factors and cytoskeletal proteins [2,4]. DNA damage response of c-Abl is mediated by Ataxia Telangiectasia Mutated (ATM) and Abl critically modulates the epigenetic and non-epigenetic regulators of DNA damage and apoptosis [5,6]. Normal c-Abl is auto-regulated both by inter and intra-molecular interactions of its N and C terminal domains [7]. The Bcr-Abl fusion protein, produced as a result of the translocation posses consistently elevated tyrosine kinase activity [8]. Normal cellular Abl p145 shuttles between nuclear and cytoplasm compartments. The fusion protein Bcr-Abl retains in the cytoplasm and activates aberrant cell signaling pathways that leads to the halt of apoptosis and induces proliferation [9]. Furthermore, Bcr-Abl protein directly or indirectly activates of Signal transducer and activator transcription 5 (STAT5)/B-cell lymphoma-extralarge (Bcl-xL), extracellular signal-regulated kinase 1/2 (Erk-1/2), phosphatidylinositide 3-kinase (PI3K)/Ak strain transforming (Akt), Src signaling molecules by Phosphorylation [9,10]. The auto-phosphorylated Bcr-Abl provides the docking site, tyr-177 of Bcr domain, for these signaling molecules [11]. Constitutively active Bcr-Abl further drives several survival pathways that provide proliferative advantage and drug resistance in CML [12]. Src kinases, such as Lyn, Hck, Fgr, gets activated downstream of Bcr-Abl signaling upon direct complex formation with the Bcr-Abl and also involved in the activation of other downstream signaling molecules thus Bcr-Abl requires Src kinases for its transforming activity [13]. Therefore, simultaneously targeting Bcr-Abl and Src kinases is proven an effective strategy by Dasatinib, a dual tyrosine kinase inhibitor [14]. Inhibition of Src family kinase (SFK) with pyrrolo pyrimidine inhibitor, A-419259, inhibits the cell growth and promote apoptosis in CML cell lines which indicates their transforming potential in CML progression [15]. The transition of chronic phase to accelerated blast phase in CML progression requires Src kinases Lyn, Hck, Fgr. Lyn plays a role in cytokine Mini Review
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