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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.
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.
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.
BCR-ABL is a constitutively active tyrosine kinase that switches on RAS, PI3K, and STAT5. Kinase-domain mutations (T315I gatekeeper) drive TKI resistance.
8 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.
Tumour-specific alteration: 2 of 2 label readouts filed under it measure a sequence variant (BCR::ABL1 T315I, BCR::ABL1 transcript (Philadelphia chromosome, quantitative PCR)) absent from normal cells. HPA BCR: RNA low tissue specificity; high antibody staining in 6 normal tissues; highest cancer staining colorectal cancer (6 of 12 high). HPA ABL1: RNA low tissue specificity; high antibody staining in 1 normal tissue; highest cancer staining carcinoid (1 of 4 high). Distribution: 1 cancer family in the corpus carries a prevalence row, label threshold or catalogue link for it (Leukaemia); approvals of single-target medicines aimed at it also list Sarcomas (soft tissue, bone, GIST), Skin cancer (all types), not counted; Open Targets associates it with 9 specific cancer types at or above 0.5 (chronic myeloid leukemia, acute lymphoblastic leukemia, gastrointestinal stromal tumor, dermatofibrosarcoma protuberans, myelodysplastic/myeloproliferative disease, myelodysplastic syndrome and more); the corpus evidence decides and the Open Targets list is quoted for comparison. (Rule 3 of scripts/fetch-target-specificity.ts.)
Sources: BCR::ABL1 T315I label threshold; BCR::ABL1 transcript (Philadelphia chromosome, quantitative PCR) label threshold; Human Protein Atlas BCR tissue; Human Protein Atlas ABL1 tissue; Open Targets ENSG00000186716 associations; Open Targets ENSG00000097007 associations
What a pathology or genomic report can say about this target, each with the thresholds approvals use.
Cell lines and mouse models for this target →
BCR-ABL is a constitutively active tyrosine kinase that switches on RAS, PI3K, and STAT5. Kinase-domain mutations (T315I gatekeeper) drive TKI resistance.
RNA: low tissue specificity, detected in all normal tissues.
Medium: Adrenal gland, Appendix, Caudate, Cerebral cortex, Cervix, Colon, Duodenum, Endometrium.
Medium only: carcinoid, cervical cancer, glioma, head and neck cancer.
HPA BCR tissue · HPA BCR pathology · HPA protein class: FDA approved drug targets
RNA: low tissue specificity, detected in all normal tissues.
Medium: Adrenal gland, Breast, Bronchus, Cervix, Colon, Duodenum, Endometrium, Epididymis.
Medium only: breast cancer, cervical cancer, colorectal cancer, endometrial cancer.
HPA ABL1 tissue · HPA ABL1 pathology · HPA protein class: FDA approved drug targets
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| 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.
Flumatinib is Hansoh Pharma's second-generation BCR-ABL inhibitor, approved in China in 2019 for newly diagnosed chronic-phase chronic myeloid leukaemia.
Nilotinib is a second-generation CML pill that produces deeper responses faster than imatinib, at the cost of cardiovascular and metabolic side effects.
Olverembatinib is Ascentage Pharma's third-generation BCR-ABL inhibitor, approved in China in 2021 for chronic myeloid leukaemia carrying the T315I mutation, and now in global phase 3 trials against the established drugs; it was the one China-only approval OnCo found missing from the headline list.
Omacetaxine (Synribo) is a twice-daily injection under the skin for chronic myeloid leukaemia that has stopped responding to at least two tyrosine kinase inhibitor pills.
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.
Query 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.
Shares Nilotinib, Imatinib, PI3K / AKT / mTOR, RAS / RAF / MEK / ERK (MAPK) and the tags driver, kinase.
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.
Shares BCR::ABL1 (Philadelphia chromosome), Resistance routes: how a blocked pathway comes back, PI3K / AKT / mTOR and the tags driver, kinase.
Shares PI3K / AKT / mTOR, RAS / RAF / MEK / ERK (MAPK) and the tags driver, kinase.
Shares STAT5 (STAT5A, STAT5B) and the tags driver, kinase.
Shares PI3K / AKT / mTOR, RAS / RAF / MEK / ERK (MAPK) and the tags driver, kinase.
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.
Shares Acute lymphoblastic leukaemia and the tags driver, fusion.