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A gene fusion that drives an aggressive leukaemia in infants and adults. It cannot be blocked directly, but the scaffold protein it depends on (menin) can. This dossier gathers the 2 products (2 approved), 96 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.
Histone H3K4 methyltransferase; fusions lose the SET domain and gain partner-driven transcriptional elongation activity. Menin binds the N-terminus and is required for leukaemogenesis.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Acute myeloid leukaemia | 5-10% | rearrangement | Higher in therapy-related AML | |
| Acute lymphoblastic leukaemia | ~80 in infants; 5-10 in adults% | rearrangement |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
| Modality | Approved |
|---|---|
| Small molecule 2 |
| Trial | Setting | Result | Products | ||
|---|---|---|---|---|---|
MATRix/IELSG43 NCT02531841 | 3 | Positive | Newly diagnosed primary central nervous system lymphoma in patients up to 70 responding to four cycles of MATRix induction: consolidation with high-dose carmustine and thiotepa and autologous stem cell transplant against two cycles of non-myeloablative rituximab, dexamethasone, etoposide, ifosfamide and carboplatin (R-DeVIC) | Three-year progression-free survival 78 percent after high-dose chemotherapy and autologous transplant against 51 percent after non-myeloablative R-DeVIC (hazard ratio 0.43, p 0.0003), with better overall survival and more toxicity. | |
| 3 | Completed | Phase 3 Open-label, Multicenter, Randomized Study of ASP2215 Versus Salvage Chemotherapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) With FLT3 Mutation | - | ||
| 3 | Active | A Phase 3, Randomized, Double-Blind Study of MK-7684A in Combination With Etoposide and Platinum Followed by MK-7684A vs Atezolizumab in Combination With Etoposide and Platinum Followed by Atezolizumab for the First-Line Treatment of Participants With Extensive-Stage Small Cell Lung Cancer (KEYVIBE-008) | - | ||
| 3 | Active | Risk-Stratified Therapy for Acute Myeloid Leukemia in Down Syndrome | - | ||
| 3 | Completed | A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of Atezolizumab Plus Carboplatin and Etoposide With or Without Tiragolumab in Patients With Untreated Extensive-Stage Small Cell Lung Cancer | - | ||
| 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 | - | ||
AHOD1331 NCT02166463 | 3 | Positive | Newly diagnosed high-risk classical Hodgkin lymphoma (stage IIB with bulk, IIIB, IVA or IVB) in patients aged 2 to 21: five cycles of brentuximab vedotin with doxorubicin, vincristine, etoposide, prednisone and cyclophosphamide against standard ABVE-PC, with PET-guided involved-site radiotherapy for slow-responding lesions | Three-year event-free survival 92.1 percent with brentuximab vedotin plus AVEPC against 82.5 percent with ABVE-PC (hazard ratio 0.41, p < 0.001), with no increase in toxicity; approved for children in the United States in November 2022. | |
CAPSTONE-1 NCT03711305 | 3 | Positive | First-line extensive-stage small cell lung cancer, China: adebrelimab or placebo plus carboplatin and etoposide | OS 15.3 vs 12.8 months, HR 0.72. | |
ACNS0333 NCT00653068 | 3 | Positive | Newly diagnosed atypical teratoid/rhabdoid tumour of the central nervous system from birth to 22 years: surgery, two courses of induction chemotherapy, three courses of high-dose chemotherapy with peripheral blood stem cell rescue and involved-field conformal radiotherapy timed by age and disease extent | Hazard of an event 0.43 compared with the historical cohort in children under 36 months (p < 0.0005); four-year event-free survival 37 percent and overall survival 43 percent for all 65 evaluable patients. | |
ACTG A5263/AMC 066 NCT01435018 | 3 | Positive | Advanced AIDS-associated Kaposi sarcoma in resource-limited settings in Africa and South America: antiretroviral therapy with paclitaxel (standard), oral etoposide or bleomycin plus vincristine, with progression-free survival at 48 weeks as the primary endpoint of a non-inferiority design | Week-48 progression-free survival 50 percent with paclitaxel against 20 percent with oral etoposide, and 64 percent against 44 percent with bleomycin plus vincristine; both investigational arms were inferior and closed early. | |
Inter-B-NHL Ritux 2010 NCT01516580 | 3 | Positive | High-risk mature B-cell non-Hodgkin lymphoma or B-acute leukaemia in patients under 18 (mostly Burkitt lymphoma): LMB chemotherapy with or without six doses of rituximab | 3-year EFS 93.9% vs 82.3%, HR 0.32; OS also improved. | |
AHL2011 NCT01358747 | 3 | Positive | Aged 16 to 60 with newly diagnosed advanced Hodgkin lymphoma: six cycles of escalated BEACOPP against a switch to ABVD after a negative scan at two cycles | Five-year progression-free survival 85.7 against 86.2 per cent when a negative interim scan allowed a switch to ABVD, with grade 3 to 4 anaemia falling from 69 to 28 per cent. | |
Alliance/CALGB 50303 NCT00118209 | 3 | Negative | Untreated diffuse large B-cell lymphoma: six cycles of dose-adjusted EPOCH-R against six cycles of R-CHOP | No difference in progression-free survival (hazard ratio 0.93) or overall survival (1.09) against R-CHOP, with substantially more febrile neutropenia, mucositis and neuropathy. | |
ANBL0531 NCT00499616 | 3 | Positive | Intermediate-risk neuroblastoma: response- and biology-based assignment to two, four or eight cycles of carboplatin, etoposide, cyclophosphamide and doxorubicin (with topotecan for poor responders) and surgery, with isotretinoin for the highest-risk subset and no chemotherapy for some stage 4S infants | Three-year event-free survival 83.2 percent and overall survival 94.9 percent with response- and biology-based reduction of chemotherapy; overall survival 100 percent for localised disease. | |
Interfant-06 NCT00550992 | 3 | Mixed | Infant ALL (<1 year): standard vs AML-type early intensification; transplant for high-risk KMT2A-rearranged infants | 6-year EFS 46.1%; intensification no benefit. | |
COG AREN0533 NCT00379340 | 3 | Positive | Stage III-IV favourable-histology Wilms tumour: response-based omission of lung radiotherapy after complete lung nodule response; augmented chemotherapy (Regimen M) for incomplete response or 1p/16q loss of heterozygosity | Overall 4-year EFS 85.4% and OS 95.6% (vs 72.5% and 84.0% in NWTS-5); 4-year EFS 90.2% for LOH 1p/16q stage III-IV with augmented therapy. | |
| 3 | Completed | A Phase III Study of Risk Directed Therapy for Infants With Acute Lymphoblastic Leukemia (ALL): Randomization of Highest Risk Infants to Intensive Chemotherapy +/- FLT3 Inhibition (CEP-701, Lestaurtinib; NSC#617807) | - | ||
EORTC/LYSA/FIL H10 NCT00433433 | 3 | Mixed | Stage I and II Hodgkin lymphoma: standard ABVD with involved-node radiotherapy against treatment adapted to the scan after two cycles, intensifying for a positive scan and dropping radiotherapy for a negative one | Switching a positive interim scan to escalated BEACOPP raised five-year progression-free survival from 77.4 to 90.6 per cent; omitting radiotherapy after a negative scan was not non-inferior in either risk group. | |
GHSG HD18 NCT00515554 | 3 | Positive | Aged 18 to 60 with newly diagnosed advanced-stage Hodgkin lymphoma: treatment intensity set by the scan after two cycles of escalated BEACOPP | Four cycles of escalated BEACOPP non-inferior to six or eight after a negative scan (five-year progression-free survival 92.2 against 90.8 per cent) with half the severe infections; adding rituximab to a positive scan arm did nothing. | |
EURAMOS-1 NCT00134030 | 3 | Negative | Resectable high-grade osteosarcoma, age up to 40: MAP induction, then randomisation by histological response (good responders: MAP vs MAP + pegylated interferon alfa-2b; poor responders: MAP vs MAPIE with ifosfamide and etoposide) | Poor responders: EFS HR 0.98 for MAPIE vs MAP, more toxicity. Good responders: no EFS benefit from interferon. | |
| 3 | Completed | A Phase III Protocol of Androgen Suppression (AS) and Radiation Therapy (RT) vs AS and RT Followed by Chemotherapy With Paclitaxel, Estramustine, and Etoposide (TEE) for Localized, High-Risk, Prostate Cancer | - | ||
GETUG 13 NCT00104676 | 3 | Positive | Poor-prognosis disseminated non-seminomatous germ cell tumours in France, the United States and Slovakia: after one cycle of BEP, patients with an unfavourable tumour marker decline were randomised to continue BEP or switch to dose-dense chemotherapy (paclitaxel-BEP-oxaliplatin then cisplatin, ifosfamide and bleomycin), with progression-free survival as the primary endpoint | Three-year progression-free survival 59 percent with marker-guided dose-dense chemotherapy against 48 percent with BEP (hazard ratio 0.66, p 0.05); salvage high-dose chemotherapy needed in 6 against 16 percent. | |
| 3 | Completed | A Randomized, Blinded, Active-control Trial of Palifermin (rHuKGF) to Evaluate Oral Mucositis in Subjects With Hematologic Malignancies Undergoing Fractionated Total Body Irradiation (fTBI) and High Dose Chemotherapy With Autologous Peripheral Blood Progenitor Cell (PBPC) Transplantation | - | ||
AEWS0031 NCT00006734 | 3 | Positive | Localised Ewing sarcoma in patients under 50: fourteen cycles of alternating vincristine, doxorubicin and cyclophosphamide with ifosfamide and etoposide given every three weeks (standard) or every two weeks with filgrastim support (interval-compressed), around local control with surgery or radiotherapy | Five-year event-free survival 73 percent with two-weekly (interval-compressed) chemotherapy against 65 percent with three-weekly chemotherapy (p 0.048), with similar toxicity. | |
JCOG9801 NCT00145002 | 3 | Mixed | Untreated aggressive adult T-cell leukaemia/lymphoma: six courses of VCAP-AMP-VECP every four weeks against eight courses of CHOP every two weeks | Complete response 40 against 25 per cent (p = 0.020) and three-year overall survival 24 against 13 per cent, with grade 4 thrombocytopenia in 74 against 17 per cent. | |
| IALT (International Adjuvant Lung Cancer Trial) | 3 | Positive | Completely resected non-small-cell lung cancer, any stage I to III: three or four cycles of cisplatin-based chemotherapy versus observation, with overall survival as the primary endpoint | Five-year survival 44.5 against 40.4 percent (hazard ratio for death 0.86). | |
| Intergroup 0096 (Turrisi): twice-daily versus once-daily thoracic radiotherapy | 3 | Positive | Limited-stage small-cell lung cancer: 45 Gy of concurrent thoracic radiotherapy delivered twice daily over three weeks versus once daily over five weeks, both starting with cycle 1 of four cycles of cisplatin and etoposide, with overall survival as the primary endpoint | Median survival 23 against 19 months (p=0.04); five-year survival 26 against 16 percent; grade 3 oesophagitis 27 against 11 percent. | |
| 3 | Active | REPLATINUM: A Phase 3, Controlled, Open-label, Global Randomized Study of RRx-001 Administered Sequentially With a Platinum Doublet or a Platinum Doublet in Third-Line or Beyond Small Cell Lung Cancer | - | ||
| 3 | Active | A Phase III, Randomised, Open-label, Global Study of Adjuvant Datopotamab Deruxtecan (Dato-DXd) in Combination With Rilvegostomig or Rilvegostomig Monotherapy Versus Standard of Care, Following Complete Tumour Resection, in Participants With Stage I Adenocarcinoma Non-small Cell Lung Cancer Who Are ctDNA-positive or Have High-risk Pathological Features (TROPION-Lung12) | - | ||
| 3 | Planned | A Single-arm, Exploratory Clinical Study Evaluating the Efficacy and Safety of Bevacizumab in Combination With Anlotinib and Etoposide as First-line Therapy for Elderly Patients With Small-cell Lung Cancer or Those Who Are Intolerant to Intensive Chemotherapy | - |
No recorded escape route names this target.
No pathway diagram carries this target as a node.
No companion diagnostic in the registry measures this target.
No model entry for this target yet; check the cancer entries on the models page.
No open questions recorded for this target yet. Suggest one.
Query for this target: (TITLE:"KMT2A MLL rearrangement" OR ABSTRACT:"KMT2A MLL rearrangement" OR TITLE:"KMT2A" OR ABSTRACT:"KMT2A" OR TITLE:"KMT2A rearrangement" OR ABSTRACT:"KMT2A rearrangement" OR TITLE:"KMT2A-rearranged" OR ABSTRACT:"KMT2A-rearranged" OR TITLE:"KMT2A-r" OR ABSTRACT:"KMT2A-r" OR TITLE:"KMT2Ar" OR ABSTRACT:"KMT2Ar") 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 KMT2A (MLL) rearrangement, not a curated reading list.
The dossier as machine-readable JSON, at /api/v1/dossiers/kmt2a.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/kmt2a.json. Licence CC BY-NC 4.0.