MLLT10
Overview
MLLT10 (MLLT10 Histone Lysine Methyltransferase DOT1L Cofactor), also known as AF10, is a transcriptional cofactor that acts as a fusion partner for KMT2A (MLL) and PICALM in acute myeloid leukemia. MLLT10 fusions dysregulate gene expression programs critical for hematopoietic differentiation. In AML, KMT2A-fusion samples carry the fewest cooperating mutations, suggesting that KMT2A–MLLT10 fusions may be sufficient to initiate disease.
Alterations observed in the corpus
- KMT2A (MLL)–MLLT10 fusion identified as one of the recurrent KMT2A fusion partners in 200 adult de novo AML cases; KMT2A-fused samples carried the fewest cooperating tier-1 mutations (mean 2.09 vs 5.24 overall; P=0.002), suggesting fusion sufficiency PMID:23634996
- PICALM–MLLT10 (PICALM–AF10) detected as a recurrent in-frame fusion by RNA-seq in the TCGA AML cohort (200 cases) PMID:23634996
Cancer types (linked)
- AML (Acute Myeloid Leukemia): KMT2A–MLLT10 and PICALM–MLLT10 fusions identified in the TCGA 200-case AML cohort; KMT2A fusions as a class were mutually exclusive of NPM1 and DNMT3A mutations (P<0.04) PMID:23634996
Co-occurrence and mutual exclusivity
- KMT2A fusions (including KMT2A–MLLT10) are mutually exclusive of NPM1 and DNMT3A mutations (P<0.04) in AML PMID:23634996
- Samples with KMT2A fusions have the fewest cooperating mutations overall (mean 2.09 vs 5.24; P=0.002) PMID:23634996
Therapeutic relevance
- KMT2A fusion-driven AML may be sensitive to DOT1L inhibitors, given MLLT10’s role as a DOT1L cofactor that activates HOX gene expression; no clinical data reported in this study PMID:23634996
Open questions
- The low cooperating-mutation burden in KMT2A-fused AML suggests fusion sufficiency for leukemogenesis, but what cooperating events do occur (and why they are selected) has not been fully characterized PMID:23634996
Sources
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