Loading
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 8 products (8 approved), 25 trials, 1 pathway 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.
BCR-ABL is a constitutively active tyrosine kinase that switches on RAS, PI3K, and STAT5. Kinase-domain mutations (T315I gatekeeper) drive TKI resistance.
| 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.
| 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.
| Modality | Approved |
|---|---|
| Small molecule 6 | |
| Small-molecule BCR-ABL1 TKI 1 | |
| Small-molecule BCR-ABL1/SRC TKI 1 |
| Trial | Setting | Result | Products | ||
|---|---|---|---|---|---|
| 3 | Active | A Phase IIIb, Multi-center, Open-label, Randomized Study of Tolerability and Efficacy of Oral Asciminib Versus Nilotinib in Patients With Newly Diagnosed Philadelphia Chromosome Positive Chronic Myelogenous Leukemia in Chronic Phase. | - | ||
| 3 | Active | A Phase III, Multi-center, Open-label, Randomized Study of Oral Asciminib Versus Investigator Selected TKI in Patients With Newly Diagnosed Philadelphia Chromosome Positive Chronic Myelogenous Leukemia in Chronic Phase | - | ||
| 3 | Completed | A Phase III Randomized Trial for Newly Diagnosed High Risk B-Lymphoblastic Leukemia (B-ALL) Including a Stratum Evaluating Dasatinib (NSC#732517) in Patients With Ph-like Tyrosine Kinase Inhibitor (TKI) Sensitive Mutations | - | ||
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%. | |
READY NCT00744497 | 3 | Negative | Chemotherapy-naive metastatic castration-resistant prostate cancer with adequate organ function, stratified by ECOG performance status, bisphosphonate use and urinary N-telopeptide: docetaxel 75 mg/m2 every 3 weeks with prednisone 5 mg twice daily, plus dasatinib 100 mg once daily or placebo, with overall survival as the primary endpoint | Median overall survival 21.5 against 21.2 months (stratified hazard ratio 0.99, 95.5 percent confidence interval 0.87 to 1.13, p=0.90): no benefit. | |
DASISION NCT00481247 | 3 | Positive | Newly diagnosed chronic-phase chronic myeloid leukaemia: dasatinib 100 mg daily against imatinib 400 mg daily | Dasatinib produced higher confirmed complete cytogenetic and major molecular response rates at 12 months than imatinib, with no difference in five-year overall survival. | |
| 3 | Recruiting | A Pivotal Registrational Phase 3 Study of Olverembatinib Combined With Chemotherapy Versus Investigator's Choice of TKI Combined With Chemotherapy in Patients With Newly Diagnosed Ph+ ALL | - | ||
| 3 | Recruiting | A Single-Arm Registrational Phase III Study of Olverembatinib in the Treatment of Patients With SDH-Deficient Gastrointestinal Stromal Tumor (POLARIS-3) | - | ||
| 3 | Completed | Molecular Profiling of Advanced Soft-tissue Sarcomas. A Phase III Study | - | ||
| 3 | - | A Study of Efficacy and Safety of Flumatinib Combined With Chemotherapy in the Treatment of Ph Positive Acute Lymphoblastic Leukemia Based on Minimal Residual Disease Monitoring | - | ||
| 3 | Recruiting | A Global, Multicenter, Open Label, Randomized, Phase 3 Registrational Study of Olverembatinib (HQP1351) in Patients With Chronic Phase Chronic Myeloid Leukemia (CML-CP) | - | ||
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%. | |
| 2 | Recruiting | Advanced solid tumours, multiple myeloma and B-cell lymphoma with a genomic alteration that an approved targeted drug addresses in another cancer: the drug is given off-label in a pragmatic basket with cohorts by drug and tumour type | Continuous cohort reporting: positive signals for pembrolizumab in high tumour mutational burden cancers and trastuzumab plus pertuzumab in ERBB2-amplified colorectal cancer; palbociclib in CDKN2A-altered lung cancer and several other matches were negative. | ||
| 2 | - | Phase II Study of Flumatinib Versus Imatinib in Adult Patients With Newly Diagnosed Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) | - | ||
| 2 | Active | A Phase II Multicenter, Open-label, Single-arm Dose Escalation Study of Asciminib Monotherapy in 2nd and 1st Line Chronic Phase - Chronic Myelogenous Leukemia (ASC2ESCALATE) | - | ||
| 2 | Recruiting | A Phase II, Multi-center, Prospective, Open-label Study of Asciminib in Patients With Chronic Myeloid Leukemia in Chronic Phase (CML-CP) or Accelerated Phase (CML-AP) With T315I Mutation Who Are Resistant, Intolerant or Ineligible to Ponatinib. | - | ||
| 2 | Completed | A Phase Ⅱ, Open Label, Single Arm, Single-Center Study to Evaluate the Efficacy and Safety of Azacitidine，Venetoclax，and Flumatinib in Newly Diagnosed Ph-positive Acute Leukemia and CML-AP/BP Patients | - | ||
| 2 | Recruiting | A Phase II, Multicenter, Open-label, Single Arm Study to Evaluate the Safety and Efficacy of Asciminib in Pediatric Participants Newly Diagnosed or Previously Treated With Philadelphia Positive Chronic Myelogenous Leukemia in Chronic Phase (Ph+ CML-CP) With or Without Known T315I Mutation | - | ||
| 2 | Recruiting | Study to Investigate Outcome of Individualized Treatment Based on Pharmacogenomic Profiling & Ex Vivo Drug Sensitivity Testing of Patient-derived Organoids in Patients With Metastatic Colorectal Cancer | - | ||
| 2 | Active | A Phase II Multi-center, Randomized, Open-label Study of Ponatinib in Chinese Patients With Chronic Myeloid Leukemia Who Have Failed Prior TKIs or With T315I Mutation, or Ph+ALL Who Have Failed Prior TKIs or With T315I Mutation | - | ||
Using Tumor Models to Determine Treatments NCT06813079 | 2 | Recruiting | ADOPT: Adaptive Organoid-Based Precision Therapy Study in Pancreatic Cancer - A Prospective Single-Arm Phase II Trial | - | |
| 1/2 | Recruiting | Open-label, Phase I/II Study to Evaluate Safety and Efficacy of Asciminib With Chemotherapy Followed by Asciminib Plus Blinatumomab in Pediatric, Adolescent, and Young Adults With Relapsed or Refractory BCR::ABL1-positive (Philadelphia Positive, Ph+) or BCR::ABL1-like (Ph-like) ALL | - | ||
| 1/2 | Recruiting | An Open-Label, Single-Arm, Phase 1/2 Study Evaluating the Safety and Efficacy of Ponatinib for the Treatment of Recurrent or Refractory Leukemias, Lymphomas or Solid Tumors in Pediatric Participants | - | ||
| 1/2 | Recruiting | A Phase Ib Study of the Safety, Pharmacokinetic of Lisaftoclax (APG-2575) Single Agent and in Combination With Homoharringtonine or Azacitidine in Patients With Relapsed/Refractory AML | - | ||
| 1/2 | Recruiting | A Multi-center, Open-label Study to Determine the Dose and Safety of Oral Asciminib in Pediatric Patients With Philadelphia Chromosome Positive Chronic Myeloid Leukemia in Chronic Phase (Ph+ CML-CP), Previously Treated With One or More Tyrosine Kinase Inhibitors | - |
No recorded escape route names this target.
KEGG's CML map is built around one fusion protein, BCR-ABL1, a kinase that never switches off and drives RAS, PI3K and STAT5 signalling. Because a single enzyme causes the disease, a single class of pill (imatinib and its successors) controls it in most patients.
Which nodes have drugs →No companion diagnostic in the registry measures this target.
| 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. |
No open questions recorded for this target yet. Suggest one.
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.
The dossier as machine-readable JSON, at /api/v1/dossiers/bcr-abl.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-NC 4.0.