BCR::ABL1 (Philadelphia chromosome)
The fusion that defines chronic myeloid leukaemia and a quarter of adult acute lymphoblastic leukaemia; the first cancer driver ever switched off by a pill.
t(9;22) creates a constitutively active ABL1 kinase. Imatinib (2001) transformed CML; dasatinib, nilotinib, bosutinib, ponatinib (covers T315I), and the allosteric STAMP inhibitor asciminib followed. In Ph+ ALL (~25% of adult B-ALL, rising with age), TKI plus chemotherapy or, increasingly, TKI plus blinatumomab without chemotherapy (D-ALBA) achieves deep molecular remissions and is reducing the need for transplant.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · The fusion that defines chronic myeloid leukaemia and a quarter of adult acute lymphoblastic leukaemia; the first cancer driver ever switched off by a pill.
- 1 · What it is
The fusion that defines chronic myeloid leukaemia and a quarter of adult acute lymphoblastic leukaemia; the first cancer driver ever switched off by a pill.
- 2 · What goes wrong in cancer
BCR-ABL is a constitutively active tyrosine kinase that switches on RAS, PI3K, and STAT5. Kinase-domain mutations (T315I gatekeeper) drive TKI resistance.
- 3 · How drugs use it
5 products aim at BCR::ABL1 (Philadelphia chromosome): small molecules. Kinases are switched on by binding ATP inside the cell, so most drugs are small molecules shaped to plug that ATP pocket.
Biology
BCR-ABL is a constitutively active tyrosine kinase that switches on RAS, PI3K, and STAT5. Kinase-domain mutations (T315I gatekeeper) drive TKI resistance.
- CML (~100%)
- Adult B-ALL (~25%; >40% over age 60)
- Paediatric B-ALL (~3%)
How common it is, by cancer
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Acute lymphoblastic leukaemia | ~25 adults; ~3 children% | t(9;22) |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Asciminib is a BCR::ABL1 blocker that binds a different pocket from every other TKI, approved for all newly diagnosed chronic myeloid leukaemia in 2024 and now being tested in Ph-positive ALL.
Bosutinib is a CML pill with less cardiovascular and pleural toxicity than its rivals; its main side effect is diarrhoea.
Dasatinib is a second-generation BCR::ABL1 pill that, combined with the immunotherapy blinatumomab, can put Ph-positive ALL into deep remission with no chemotherapy at all.
Nilotinib is a second-generation CML pill that produces deeper responses faster than imatinib, at the cost of cardiovascular and metabolic side effects.
Ponatinib is the only BCR::ABL1 inhibitor that covers the T315I resistance mutation. In 2024 it became the preferred pill for newly diagnosed Ph-positive ALL.
IRIS made imatinib the first-line standard for CML worldwide and established the tyrosine kinase inhibitor as a chronic, life-long oral therapy. For most patients CML became a manageable condition with near-normal life expectancy. Later generations of TKIs (dasatinib, nilotinib, asciminib) produce faster, deeper responses but have not shown a survival advantage over imatinib.
Druker's 2001 imatinib paper turned the idea of hitting a cancer's specific molecular engine into a working medicine. For people with CML it began the shift from a fatal disease treated with interferon or transplant to one managed with a daily tablet. It also set expectations, later tempered, that every cancer might have its own imatinib.
Latest papers
topQuery for this target: (TITLE:"BCR::ABL1" OR ABSTRACT:"BCR::ABL1" OR TITLE:"Philadelphia chromosome" OR ABSTRACT:"Philadelphia chromosome" OR TITLE:"BCR-ABL1" OR ABSTRACT:"BCR-ABL1") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about BCR::ABL1 (Philadelphia chromosome), not a curated reading list.
Pages like this
not linked directly; found by shared links- TargetKIT
Shares Nilotinib, Imatinib, PI3K / AKT / mTOR, RAS / RAF / MEK / ERK (MAPK) and the tags driver, kinase.
- TargetALK
Shares Drivers, passengers & the two-hit model, Resistance routes: how a blocked pathway comes back, PI3K / AKT / mTOR, RAS / RAF / MEK / ERK (MAPK) and the tags driver, kinase.
- TargetROS1
Shares PI3K / AKT / mTOR, RAS / RAF / MEK / ERK (MAPK) and the tags driver, kinase.
- TargetFGFR2
Shares PI3K / AKT / mTOR, RAS / RAF / MEK / ERK (MAPK) and the tags driver, kinase.
- TargetPIK3CA / PI3K-alpha
Shares Resistance routes: how a blocked pathway comes back, PI3K / AKT / mTOR and the tags driver, kinase.
- TargetBRAF
Shares Drivers, passengers & the two-hit model, RAS / RAF / MEK / ERK (MAPK) and the tags driver, kinase.
- TargetEGFR
Shares Drivers, passengers & the two-hit model, Resistance routes: how a blocked pathway comes back, PI3K / AKT / mTOR, RAS / RAF / MEK / ERK (MAPK) and the tags driver, kinase.
- TargetKMT2A (MLL) rearrangement
Shares Acute lymphoblastic leukaemia and the tags driver, fusion.