- Philadelphia chromosome - Karyotyping
- BCR-ABL fusion protein - FISH
- 9 to 22 chromosomal translocation
- c-ABL is tyrosine kinase, BCR-ABL makes it constituitively active no longer under GF control
- Causes Chronic Myeloid Leukaemia (In mature myeloid cells)
- Excess proliferation of cells due to BCR2 inhibiting apoptosis, JAK/STAT/ and Ras/MAPK induce proliferation
- Can progress to Acute Myeloid Leukaemia (In blast cells) and very resistant to Imatinib at this stage as ^ BCR-ABL
- Resistance due to different point mutations in BCR-ABL gene- evolving cancer?
- Imatinib: Nicholas Lydon, late 1990s based on phenylaminopyrimidine (added methyl and benzamide), Dasatinib is second generation drug.
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