Carcinogenesis of Bcr-Abl in CML

Mechanisms of carcinogenesis of Bcr-Abl in CML. Oligomerization and cross-phosphorylation (P) of Bcr-Abl fusion proteins (top) leads to constitutive activation of the Abl kinase domain. This leads (bottom) to activation of three key pro-survival pathways, STAT5 (signal transducer and activator of transcription 5), which leads to increased expression of anti-apoptotic Bcl-xL, the Raf → ERK (extracellular signal-regulated kinase, or MAP kinase) pathway, which increases expression of anti-apoptotic Bcl2, and the phosphoinositide-3 kinase → Akt pathway, a major anti-apoptotic pathway in cancer cells and cardiomyocytes, that inhibits pro-apoptotic factors FOXO3a and Bad. This culminates in potent inhibition of apoptosis in CML cells.

Publication

Mechanisms of cardiomyopathy associated with tyrosine kinase inhibitor cancer therapeutics. () Ming Hui Chen, et al. Circulation. ;118(1):84-95. Figure: F1. Homo sapiens

Disease mentions