- 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
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: