Gene affected:
'KMT2A - Histone-lysine N-methyltransferase 2A (also acute lymphoblastic leukemia 1 (ALL-1), myeloid/lymphoid or mixed-lineage leukemia 1)

Clinical significance
The partial tandem duplication of KMT2A gene (previously MLL-PTD) variably involves different exons and is not detected by cytogenetics. Lesions occur in both AML and MDS.
  • KMT2A is also involved in fusion with a range of other genes through balanced translocations that are detected using standard cytogenetic testing.
  • Both the cytogenetic-detected translocations and the NGS-detected PTD are associated with poorer prognosis.

Function of gene

KMT2A encodes a transcriptional coactivator that plays an essential role in regulating gene expression during hematopoiesis. Its function includes histone H3 lysine 4 methyltransferase activity which mediates chromatin modifications associated with epigenetic transcriptional activation. Multiple chromosomal translocations involving this gene are associated with acute myeloid and lymphoid leukaemias

NGS panel gene coverage

Exons 1-12 & 27, introns 2-5 & 8-12


AML (15-11% of adult AML - rare in children)
Associated with poor outcome. Often affecting older patients (usually presents as FAB M1 and M2) with fewer additional cytogenetic events. De novo KMT2A-PTD AML patients (excluding patients with underlying MDS) may show better results.
MDS (approx. 6-7%)
Particularly in association with leukaemic transformation, often presenting as high grade disease with excess blasts and a typically normal karyotype

NOTE: Analysis of a cohort of patients with KMT2A PTD mutations (n=90) showed a very high prevalence (>85%) of alterations in epigenetic regulator genes, supporting the concept that treatment based on demethylating agents or histone-deacetylase inhibitors might be an option in patients harbouring MLL-PTD


GeneWiki link:
Gene Wiki entry for KMT2A
1. ref1 Links to epigenetic regulator genes
2. Outcome in MDS