# KMT2A (MLL) rearrangement

Source: https://onco.cc/targets/kmt2a/  
OnCo record `kmt2a` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Target
- Last checked: 2026-09-07
- Also known as: KMT2A rearrangement; KMT2A-rearranged; KMT2A-r; KMT2Ar; KMT2A fusion; MLL-rearranged; MLL rearrangement; MLLr; MLL-r; 11q23 rearrangement; KMT2A partner gene
- Tags: driver; fusion
- Symbol: KMT2A
- Class: transcription
- 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.
- Where found: Infant ALL (~80%); Adult AML (5-10%; therapy-related after topoisomerase II inhibitors); Adult B-ALL (KMT2A::AFF1); Mixed-phenotype acute leukaemia

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/KMT2A
- Wikipedia: https://en.wikipedia.org/wiki/KMT2A

## Connected records

- targets: [HOXA9](https://onco.cc/targets/hoxa9/), [MEIS1](https://onco.cc/targets/meis1/), [Menin](https://onco.cc/targets/menin/)
- cancers: [Acute lymphoblastic leukaemia](https://onco.cc/cancers/all-leukemia/), [Acute myeloid leukaemia](https://onco.cc/cancers/aml/), [Acute myeloid leukaemia in children](https://onco.cc/cancers/aml-paediatric/), [Infant acute lymphoblastic leukaemia (KMT2A-rearranged, under one year)](https://onco.cc/cancers/all-infant/), [NPM1-mutated and KMT2A-rearranged acute myeloid leukaemia](https://onco.cc/cancers/aml-npm1-kmt2a/)
- drugs: [Etoposide](https://onco.cc/drugs/etoposide/), [Revumenib](https://onco.cc/drugs/revumenib/), [Ziftomenib](https://onco.cc/drugs/ziftomenib/)
- terms: [B-ALL risk groups (NCI criteria, ETV6::RUNX1, hyperdiploidy, hypodiploidy, iAMP21, IKZF1, CNS status)](https://onco.cc/terms/b-all-cytogenetic-risk/), [ELN 2022 risk classification](https://onco.cc/terms/eln-risk/)
- trials: [AUGMENT-101](https://onco.cc/trials/augment-101/), [Interfant-06](https://onco.cc/trials/interfant-06/)
- pairings: [Menin inhibitor + venetoclax + azacitidine](https://onco.cc/pairings/menin-plus-venetoclax-hma/)
- ideas: [Group trials by broken mechanism, not by organ or single mutation](https://onco.cc/ideas/idea-bio2-mechanism-defined-baskets/), [Menin inhibitors for infant KMT2A-rearranged ALL](https://onco.cc/ideas/idea-menin-infant-all/)
- bottlenecks: [Rare and paediatric cancers without markets](https://onco.cc/bottlenecks/b-rare-cancers/), [The undruggable drivers](https://onco.cc/bottlenecks/b-undruggable-targets/)
- pathways: [Epigenetic reprogramming](https://onco.cc/pathways/epigenetic-reprogramming/), [Transcriptional machinery & addiction](https://onco.cc/pathways/transcription-addiction/)
- key papers: [AUGMENT-101: revumenib, the first menin inhibitor, in relapsed leukaemias driven by KMT2A rearrangement or NPM1 mutation](https://onco.cc/key-papers/paper-augment-101-revumenib-menin-nature-2023/)

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