Breakpoint cluster region-Abelson murine leukemia viral oncogene fusion protein and Src family kinase (BCR-ABL and Src (or, more commonly, BCR-ABL; Src family kinases))

The BCR-ABL fusion protein is an oncogenic, constitutively active tyrosine kinase produced by the translocation between chromosomes 9 and 22 (the Philadelphia chromosome) and is the primary driver of chronic myeloid leukemia and related leukemias[4][8][6]. It includes regulatory domains from both BCR and Abl1, leading to deregulated cell signaling, uncontrolled cell proliferation, and inhibited apoptosis[4][2][6]. Src family kinases are a group of cytoplasmic non-receptor tyrosine kinases (including Src, Lyn, Fyn, Yes, Hck, Fgr, Blk, Lck, Yrk) involved in signal transduction pathways modulating cell growth, differentiation, survival, and immune function[1][2]. In BCR-ABL-positive leukemias, Src family kinases often cooperate with or are modulated by BCR-ABL, contributing to cell transformation and disease progression[1][4][5]. Therapeutic inhibition of BCR-ABL and/or Src family kinases with small molecule TKIs has revolutionized CML and Ph+ ALL treatment, but clinical management is challenged by drug resistance mutations, off-target effects, and complex kinase interaction networks[5][8].

Other names

BCR-ABL (sometimes BCR::ABL, BCR-ABL1, Philadelphia chromosome fusion protein)Src family kinases (Src, Fyn, Yes, Lyn, Hck, Fgr, Blk, Lck, Yrk)Abelson murine leukemia viral oncogene homolog 1 (ABL1)Breakpoint cluster region (BCR)Philadelphia chromosome tyrosine kinase

Competitive inhibition of ATP binding in the kinase domain - Blockade of tyrosine phosphorylation activity, shutting down oncogenic signaling[5][8] - Induction of apoptosis and inhibition of cell proliferation - Inhibition of downstream adaptors and transcription factors (e.g., STAT5 and Crkl)[8]