Molecular markers
KMT2A (MLL)
Author: Nat Pernick, M.D.
Last author update: 1 November 2013
Last staff update: 24 October 2022
Copyright: 2003-2024, PathologyOutlines.com, Inc.
PubMed Search: MLL KMT2A
Cite this page: Pernick N. KMT2A (MLL). PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainsmll.html. Accessed July 15th, 2024.
Definition / general
- Gene at 11q23 called MLL (mixed lineage leukemia), ALL1, HRX and Htrx (from Drosophila trithorax protein)
- Note: ALL1 may also signify Allergen 1 gene in Cryptococcus (Mol Microbiol 2013;88:713)
Pathophysiology
- A histone H3 methyltransferase (GeneCards)
- Epigenetic transcriptional regulator that controls proliferative expansion of immature hematopoietic progenitors in part by methylating histone 3 on lysine 4
- Required for normal development, but also mutated in subset of aggressive human leukemias
- Epigenetics: study of heritable changes in gene expression or chromosome stability that don't alter the underlying DNA sequence; epigenetic changes are established through DNA methylation, non-coding RNAs and covalent modification of specific residues on histone proteins (Cancers (Basel) 2012;4:904)
- Genetic alterations found in pediatric (particularly infant) and 5-10% of adult de novo and therapy-related acute lymphoblastic leukemias or acute myeloblastic leukemia (Haematologica 2013;98:825)
Clinical features
MLL tumors:
Rarely associated with intravascular diffuse large B cell lymphoma (Arch Pathol Lab Med 2009;133:1477)
- See these PathologyOutlines.com topics:
- Accounts for 5-10% of acute leukemias, usually M4 or M5
- Aggressive clinical features and poor outcome
- MLL tumors usually CD19+, CD10-, with lymphoid and myeloid markers
- Over 100 MLL gene rearrangements in acute leukemia, but 7 rearrangements account for 90%: AFF1/AF4, MLLT3/AF9, MLLT1/ENL, MLLT10/AF10, ELL, partial tandem duplications (MLL PTDs) and MLLT4/AF6 (Leukemia 2013;27:2165)
- t(4;11)(q21;q23) [MLL-AF4]:
- Associated with pro-B immunophenotype - fusion gene detectable in most pro-B ALL cases in infancy, but only in 30–40% of adults
- Bone marrow transplantation recommended in childhood MLL with t(4;11)(q23;q23) due to otherwise poor prognosis
- MLL gene also frequently rearranged in secondary leukemias (PLoS One 2013;8:e75871)
