MLLT3

Overview

MLLT3 (MLLT3 Super Elongation Complex Subunit), also known as AF9, is a transcription elongation factor and chromatin-binding protein. MLLT3 is a recurrent KMT2A (MLL) fusion partner in acute myeloid leukemia. As a component of the super elongation complex and DOT1L complex, KMT2A–MLLT3 fusions drive aberrant HOX gene expression and block myeloid differentiation. KMT2A-fused AML samples carry the fewest cooperating tier-1 mutations, suggesting the fusion itself is a potent oncogenic driver.

Alterations observed in the corpus

  • KMT2A (MLL)–MLLT3 (AF9) fusion identified as one of the recurrent KMT2A fusion partners among 11 KMT2A-fused cases in 200 adult de novo AML cases (TCGA AML cohort); KMT2A-fused samples had mean 2.09 cooperating tier-1 mutations vs 5.24 overall (P=0.002) PMID:23634996
  • MLLT3-KMT2A (t(9;11)) fusion in AML appears favorable relative to other KMT2A fusions; KMT2A fusions overall present in 3% (n=44) of the cohort with multiple partners PMID:27276561

Cancer types (linked)

  • AML (Acute Myeloid Leukemia): KMT2A–MLLT3 is among the most common KMT2A rearrangements; detected in the TCGA 200-case AML cohort; KMT2A fusions as a class are mutually exclusive of NPM1 and DNMT3A mutations (P<0.04) PMID:23634996

Co-occurrence and mutual exclusivity

  • KMT2A fusions (including KMT2A–MLLT3) are mutually exclusive of NPM1 and DNMT3A mutations (P<0.04) in AML PMID:23634996
  • KMT2A-fused AML (as a class) has the fewest cooperating tier-1 mutations, consistent with strong oncogenic sufficiency of the fusion PMID:23634996

Therapeutic relevance

  • KMT2A–MLLT3 fusion-driven AML may be sensitive to DOT1L inhibitors or super elongation complex inhibitors; no clinical data reported in this study PMID:23634996

Open questions

  • The precise incidence of KMT2A–MLLT3 versus other KMT2A partners in this cohort is not broken down by individual partner in the available data; relative cooperating mutation patterns per partner type require larger cohorts PMID:23634996

Sources

This page was processed by entity-page-writer on 2026-05-15. - PMID:27276561

This page was processed by entity-page-writer on 2026-05-15.