BCR-ABL tyrosine kinase and SRC-family protein tyrosine kinases (BCR-ABL and SFKs)

BCR-ABL tyrosine kinase is an oncogenic fusion protein resulting from a reciprocal translocation between chromosomes 9 and 22, known as the Philadelphia chromosome, characteristic of chronic myelogenous leukemia (CML) and some acute lymphoblastic leukemias (ALL)[7]. BCR-ABL possesses constitutive tyrosine kinase activity that drives uncontrolled cell proliferation, survival, and transformation by activating multiple downstream pathways such as STAT5 and CRKL[5][7]. SRC-family kinases are a group of non-receptor cytoplasmic tyrosine kinases—such as SRC, LYN, HCK, and FYN—that participate in signal transduction related to cell growth, migration, and survival[6]. In BCR-ABL-driven leukemias, SRC-family kinases are often activated by BCR-ABL, and inhibition of both kinase families may induce apoptosis and inhibit growth more effectively[3][6]. Targeted kinase inhibitors (TKIs) such as imatinib, dasatinib, and nilotinib have dramatically improved outcomes for patients with CML and Ph+ ALL by specifically blocking BCR-ABL activity; drugs like dasatinib also inhibit SRC-family kinases. Ongoing challenges include mutation-driven resistance, adverse effects from broad kinase inhibition (especially with multi-target TKIs), and the need for biomarkers to monitor treatment response[4][5][9].

Other names

BCR::ABLPhiladelphia chromosome fusion proteinBCR-ABL1SRCHCKLYNFYNYESBLKFGRLCK

Competitive inhibition of ATP binding at the kinase domain - Inhibition of phosphorylation activity, leading to reduced downstream oncogenic signaling - Induction of apoptosis and cell cycle arrest in leukemia cells[5]