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BCR-ABL, KIT, PDGFRβ
- Target
- BCR-ABL, KIT, PDGFRβ
- Molecular classification
- Tyrosine kinase, Receptor tyrosine kinase, Oncoprotein, Enzyme
01
Overview
The BCR-ABL fusion protein results from the Philadelphia chromosome translocation, creating a constitutively active tyrosine kinase that drives chronic myeloid leukemia by activating multiple signaling pathways (RAS/MAPK, PI3K/AKT/mTOR) and promoting unchecked cell proliferation and survival. KIT and PDGFRβ are receptor tyrosine kinases involved in normal cellular signaling and development; mutations or dysregulation drive oncogenesis in several cancers by similar mechanisms. Targeted kinase inhibitors such as imatinib revolutionized therapy for CML and other malignancies by selectively blocking these aberrant kinases, though resistance and disease persistence remain clinical challenges.
- Other names
- Philadelphia chromosomePh fusion proteinBCR-ABL1c-KITCD117Stem cell factor receptorPDGFRBCD140bBeta-type platelet-derived growth factor receptor
02
Mechanism of action
Competitive inhibition of the ATP-binding site of the kinase domain; Prevention of phosphorylation of downstream signaling proteins; Inhibition of cell proliferation and induction of apoptosis
03
Biological functions
Signal transductionCell proliferationCell survival (apoptosis inhibition)Cell cycle controlDifferentiationCytoskeleton organization
04
Disease associations
Cancer (notably Chronic Myeloid Leukemia for BCR-ABL, GIST and AML for KIT, and various sarcomas and leukemias for PDGFRβ)Other: Mutations in KIT and PDGFRβ also occur in other malignancies
05
Safety considerations
Resistance mutations (especially T315I in BCR-ABL, D816V in KIT)Off-target toxicities (myelosuppression, skin rashes, cardiovascular side-effects)Persistence of leukemic stem cells despite kinase inhibition
06
Interacting drugs
5 more in the full profile.
07
Biomarkers
BCR-ABL1 transcript levels (quantitative PCR for CML monitoring)Ph chromosome detection (cytogenetics)KIT and PDGFRβ mutations (sequencing panels in tumors)
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