KMT2a-rearranged acute leukaemias — insights and potential therapeutic options
Year: 2025
Type: article
Abstract: The lysine methyltransferase 2A (KMT2A) protein is a histone lysine 4 (H3K4) methyltransferase that is involved in normal development through supporting certain gene transcriptions. On the other hand, it is rather a ‘promiscuous’ protein that is involved in fusion with a variety of partner proteins creating an altered mixed lineage leukaemia complex that is not expressed in normal cells and is involved in the transformation of normal haematopoietic cells to leukaemic ones. To date, more than 120 fusion partners have been identified. They account for 5–10% of all acute leukaemias. Of these, infants account for more than 70% of the total cases. Another subgroup of acute leukaemia patients with the KMT2A-rearrangement develops it as a result of exposure to certain types of chemotherapeutic agents. The outcome of KMT2A-rearranged acute leukaemia is usually very poor especially when compared to other patients without the KMT2A-rearrangement. They are often chemo-resistant and display cell plasticity. This has prompted a search for better therapies. At the same time, more research has led to elucidation of the KMT2A fusion protein complexes and its involvement in leukaemic transformation. This article reviews the biology of the KMT2A protein and the role played by some of the partner proteins in the development of acute leukaemias. It also considers cell plasticity in KMT2A-rearranged leukaemia, and finally some promising therapeutics that could impact upon the management landscape of KMT2A-rearranged acute leukaemias.
Source: Acta Haematologica Polonica
DOI: 10.5603/ahp.102873
Author: Ogochukwu Izuegbuna
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4408228707