Philadelphia chromosome (Ph+, BCR::ABL1)
A swapped piece between chromosomes 9 and 22 that fuses two genes into BCR::ABL1, a runaway kinase. It causes chronic myeloid leukaemia and a hard-to-treat quarter of adult acute lymphoblastic leukaemia, and was the target of imatinib, the first modern targeted cancer drug.
Described by Nowell and Hungerford in 1960 and explained by Rowley in 1973, the Philadelphia chromosome defines CML and Ph+ ALL. Imatinib (2001) turned CML into a chronic condition with near-normal life expectancy; dasatinib, nilotinib, bosutinib, ponatinib (covers T315I) and asciminib (allosteric) followed. In Ph+ ALL, TKIs plus chemotherapy or chemotherapy-free TKI plus blinatumomab (GIMEMA D-ALBA) now cure most patients without transplant. Ph-like ALL has a similar gene expression signature without the fusion and responds to some of the same drugs. Detected by karyotype, FISH or PCR for the fusion transcript.
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not linked directly; found by shared links- TermPh-positive ALL
Shares Asciminib, Ponatinib, Dasatinib, Blinatumomab.
- PairingBCR::ABL1 TKI + blinatumomab (chemotherapy-free Ph+ ALL)
Shares Ponatinib, Dasatinib, Blinatumomab, Acute lymphoblastic leukaemia.
- IdeaTransplant-free Ph-positive ALL for MRD-negative adults
Shares Ponatinib, Dasatinib, Blinatumomab, Acute lymphoblastic leukaemia.
- TermOn-target resistance mutations (gatekeeper, solvent-front, compound)
Shares Asciminib, Ponatinib, Tyrosine kinase inhibitor (TKI).
- Key paperIRIS: imatinib versus interferon plus cytarabine as first treatment for chronic myeloid leukaemia
- TrialPhALLCON
Shares Ponatinib, Imatinib, Acute lymphoblastic leukaemia.
- TrialD-ALBA (GIMEMA LAL2116)
Shares Dasatinib, Blinatumomab, Acute lymphoblastic leukaemia.
- TargetBCR::ABL1 (Philadelphia chromosome)