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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.
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.
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.
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.
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.
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.
Broadly expressed or essential: HPA finds the RNA at low tissue specificity; the 3 medicines aimed at it (Revumenib, Ziftomenib, Etoposide) act on the wild-type protein, so normal tissue is exposed and the therapeutic window comes from the tumour's faster division or its dependence on the protein. HPA KMT2A: RNA low tissue specificity; high antibody staining in 2 normal tissues; highest cancer staining head and neck cancer (2 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 Testicular germ cell tumours, Lung cancer (all types), Sarcomas (soft tissue, bone, GIST), Lymphoma and more, not counted; Open Targets associates it with 0 specific cancer types at or above 0.5. (Rule 7 of scripts/fetch-target-specificity.ts.)
Sources: Human Protein Atlas KMT2A tissue; Open Targets ENSG00000118058 associations
First described 1992. Earliest sequence paper UniProt cites for the protein: Tkachuk D.C. et al, Cell, 1992, "Involvement of a homolog of Drosophila trithorax by 11q23 chromosomal translocations in acute leukemias". Source.
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.
RNA: low tissue specificity, detected in all normal tissues.
Medium: Adrenal gland, Appendix, Bone marrow, Breast, Bronchus, Cerebellum, Cerebral cortex, Cervix.
Medium only: carcinoid, liver cancer, melanoma, pancreatic cancer.
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 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.
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.
Shares Menin inhibitor + venetoclax + azacitidine, MEIS1, HOXA9, AUGMENT-101 and the tag driver.
Shares MEIS1, HOXA9, Ziftomenib, Revumenib.
Shares Acute lymphoblastic leukaemia and the tags driver, fusion.
Shares MEIS1, HOXA9, Ziftomenib, Revumenib.
Shares The undruggable drivers and the tag driver.
Shares AUGMENT-101, AUGMENT-101: revumenib, the first menin inhibitor, in relapsed leukaemias driven by KMT2A rearrangement or NPM1 mutation, Revumenib, Menin.
Shares ELN 2022 risk classification, Acute myeloid leukaemia in children, Acute myeloid leukaemia and the tag driver.
Shares AUGMENT-101, AUGMENT-101: revumenib, the first menin inhibitor, in relapsed leukaemias driven by KMT2A rearrangement or NPM1 mutation, Revumenib, Menin.