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. This dossier gathers the 5 products (5 approved), 2 trials, 0 pathways and 0 resistance routes in the corpus that involve it, with external identifiers so it can be joined to UniProt, ChEMBL, Open Targets and the rest of biology.
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%)
Elsewhere: identifiers and databases
Built from HGNC, Ensembl, UniProt and ChEMBL idsHow common it is, by cancer
Full matrix →| 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.
Mutation hotspots and which drugs address them
| Residue | Kind | How common | What it does | Addressed by | Defeats | Source |
|---|---|---|---|---|---|---|
| T315I (gatekeeper) 315 | Resistance | not sourced | Blocks imatinib, dasatinib, nilotinib and bosutinib. Ponatinib was designed for it; asciminib (allosteric, myristoyl pocket) is active at higher doses. | Soverini et al., Blood 2011 | ||
| P-loop (G250E, Y253H, E255K/V) 253 | Resistance | not sourced | Destabilise the inactive conformation imatinib and nilotinib bind; dasatinib and ponatinib retain activity. | Soverini et al., Blood 2011 | ||
| F317L / V299L 317 | Resistance | not sourced | Dasatinib-contact residues; nilotinib and bosutinib remain options. | Soverini et al., Blood 2011 | ||
| A337 / P465 / V468 (myristoyl pocket) 465 | Resistance | not sourced | Allosteric-site mutations selected by asciminib; the ATP-site inhibitors are unaffected, the logic behind combining the two classes. | Soverini et al., Blood 2011 |
Frequencies are quoted from the source on each row; a blank means no figure was sourced, not that it is rare. Domain boundaries are approximate. Sources for the map: COSMIC: ABL1.
Products by modality and phase
Browse products →Trials
Evidence ranking →| Trial | Phase | Status | Setting | Result | Products |
|---|---|---|---|---|---|
| PhALLCON NCT03589326 | 3 | Positive | Newly diagnosed Ph-positive ALL, adults: ponatinib vs imatinib, each with reduced-intensity chemotherapy | MRD-negative CR 34.4% vs 16.7%. | |
| D-ALBA (GIMEMA LAL2116) NCT02744768 | 2 | Positive | Newly diagnosed Ph-positive ALL, adults of all ages: dasatinib induction followed by blinatumomab, no systemic chemotherapy | 18-month OS 95%, DFS 88%. |
Resistance routes that involve this target
Unaddressed routes →The resistance atlas has no route that names this target.
Pathways where it is a node
Pathway-to-drug matrix →No pathway diagram carries this target as a node.
Companion diagnostics and assays
Assay registry →No companion diagnostic in the registry measures this target.
Preclinical models
All models →| Cell line | Identifiers | Why it is used |
|---|---|---|
| K-562 | CVCL_0004 · ACH-000551 | CML blast crisis, BCR::ABL1 (b3a2); the original imatinib line and the CAR-T negative-control target. |
| KU812 | CVCL_0379 · ACH-000074 | CML basophilic line, BCR::ABL1. |
| KCL-22 | CVCL_2091 · ACH-000983 | CML line that acquires T315I under imatinib in culture. |
| SUP-B15 | CVCL_0103 · ACH-000059 | Ph-positive ALL, p190. |
| Ba/F3 BCR-ABL1 mutants | not resolved | T315I, E255K, Y253H and myristoyl-pocket panels. |
- Retroviral BCR-ABL bone-marrow transplant (p210 BCR-ABL1 in transplanted marrow) Mouse Tumor Biology database (JAX)
Open questions
All open questions →No open questions recorded for this target yet. Suggest one.
Ideas and companies
Key papers and the live literature
Preprints →- IRIS: imatinib versus interferon plus cytarabine as first treatment for chronic myeloid leukaemia · New England Journal of Medicine 2003
- First imatinib trial: a pill that switched off the enzyme driving chronic myeloid leukaemia · New England Journal of Medicine 2001
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.
Export
The dossier as machine-readable JSON: identifiers from HGNC, Ensembl, UniProt and ChEMBL, products with status, trials, pathways, hotspots, open questions and assays. The full entity record is in the open API at /api/v1/entities/bcr-abl.json. Licence CC BY 4.0.