KMT2A (MLL) rearrangement
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.
KMT2A (formerly MLL) rearrangements with >80 partner genes occur in ~5-10% of adult AML (higher in therapy-related AML), ~80% of infant ALL, and a subset of adult B-ALL. The fusion protein needs menin to bind chromatin and sustain HOXA9/MEIS1 expression. Menin inhibitors revumenib (approved 2024) and ziftomenib (in trials for KMT2Ar) release the differentiation block. Resistance emerges through MEN1 mutations at the drug-binding site.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · 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.
- 1 · What it is
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.
- 2 · What goes wrong in cancer
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.
- 3 · How drugs use it
2 products aim at KMT2A (MLL) rearrangement: small molecules. Transcription factors have no pocket to plug, so drugs either degrade them or block the partner protein they need to dock on DNA.
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.
- Infant ALL (~80%)
- Adult AML (5-10%; therapy-related after topoisomerase II inhibitors)
- Adult B-ALL (KMT2A::AFF1)
- Mixed-phenotype acute leukaemia
How common it is, by cancer
| 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.
Etoposide is a chemotherapy from the mayapple plant, essential to curing testicular cancer (BEP), treating small-cell lung cancer, lymphomas, childhood sarcomas and leukaemias, and used in transplant conditioning.
Ziftomenib is the second menin inhibitor for leukaemia, approved in November 2025 as a once-daily pill for relapsed NPM1-mutated AML.
Latest papers
topQuery for this target: (TITLE:"KMT2A MLL rearrangement" OR ABSTRACT:"KMT2A MLL rearrangement" OR TITLE:"KMT2A" OR ABSTRACT:"KMT2A") 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.
Pages like this
not linked directly; found by shared links- TargetNPM1 mutation
Shares AUGMENT-101, Menin inhibitor + venetoclax + azacitidine, ELN 2022 risk classification, AUGMENT-101: revumenib, the first menin inhibitor, in relapsed leukaemias driven by KMT2A rearrangement or NPM1 mutation and the tag driver.
- TargetBCR::ABL1 (Philadelphia chromosome)
Shares Acute lymphoblastic leukaemia and the tags driver, fusion.
- TargetKRAS
Shares The undruggable drivers and the tag driver.
- TargetIDH1 / IDH2
Shares Group trials by broken mechanism, not by organ or single mutation, Epigenetic reprogramming, Acute myeloid leukaemia and the tag driver.
- TargetFLT3
Shares ELN 2022 risk classification, Acute myeloid leukaemia and the tag driver.
- TermDifferentiation syndrome
Shares AUGMENT-101, Ziftomenib, Revumenib, Menin.
- TargetNTRK
Shares Rare and paediatric cancers without markets and the tag driver.
- TargetRET
Shares Rare and paediatric cancers without markets and the tag driver.