Other tyrosine kinases involved in CML signaling

Other tyrosine kinases involved in CML signaling refers to a heterogeneous group of enzymes, primarily including the Src family kinases (SFKs) such as LYN, HCK, and FGR, as well as AXL and JAK2, which contribute to the pathophysiology of Chronic Myeloid Leukemia (CML) (Donato et al., 2003, Blood; Samanta et al., 2006, Cancer Res). While the BCR-ABL1 fusion protein is the hallmark driver of CML, these additional kinases facilitate bypass signaling pathways that promote leukemic cell survival, proliferation, and genomic instability. They are particularly significant in the context of therapeutic resistance; for instance, overactivation of LYN kinase has been identified as a mechanism of imatinib resistance that does not involve BCR-ABL1 mutations (Gioia et al., 2011, Blood). Drugs like dasatinib and bosutinib were specifically designed to target both BCR-ABL1 and SFKs to provide broader therapeutic coverage and overcome such resistance (FDA, Dasatinib/Bosutinib Prescribing Information). Furthermore, some of these kinases are involved in the maintenance of leukemic stem cells, making them targets for achieving deep molecular responses and potential treatment-free remission.

Other names

Non-BCR-ABL tyrosine kinasesSrc family kinases in CMLSecondary CML signaling kinasesBypass kinases in CMLNon-BCR-ABL1 tyrosine kinases

Inhibition of non-BCR-ABL tyrosine kinases (e.g., Src family, AXL, JAK2) to disrupt parallel or downstream signaling pathways that contribute to leukemic cell survival and TKI resistance.