A study has revealed how mutations in the ASXL1 gene trigger the development of clonal haematopoiesis.
The study shows how mutations in the gene affect blood cell development, growth and function, researchers have reported. Mutations in ASXL1 are “very common” in clonal haematopoiesis (CH), they say – one of the top three mutations in CH, alongside DNMT3A and TET2. However, it wasn’t known exactly how ASXL1 mutations cause CH.
The study at La Jolla Institute for Immunology, California, USA, used laboratory mice to examine the effects of ASXL1 mutations. This showed a big impact on the normal working of ‘heterochromatin’ DNA, which normally protects the development of blood cells. The mutations “spell disaster” for heterochromatin activity, the researchers say, preventing the maturation of haematopoietic stem cells.
This is caused by proteins from the mutated ASXL1 interacting with the EHMT1-EHMT2 histone methyltransferase protein complex. This leads to the uncoiling of the heterochromatic DNA and allowing the activation of genes, including so-called ‘jumping’ genes, that would otherwise be silent.
The findings have been reported in the journal Proceedings of the National Academy of Sciences.
Researcher Dr Zhen Dong said: “We know that many diseases – and all cancers – are driven by mutations in the genome. We showed how mutated ASXL1 may give rise to dysfunctional cells in your bone marrow and blood.”
The researchers continue to explore further interactions between ASXL1 and the immune system. They are now examining the impact on the TET2 protein, which is also frequently found to be mutated in blood cancers.
Source:
Dong Z, Sepulveda H, Arteaga-Vazquez LJ, Blouin C, Fernandez J, Binder M, Chou WC, Tien HF, Patnaik MM, Faulkner GJ, Myers SA, Rao A. (2025) “A mutant ASXL1-EHMT complex contributes to heterochromatin dysfunction in clonal hematopoiesis and chronic monomyelocytic leukemia.” Proceedings of the National Academy of Sciences, 3 January 2025, doi: 10.1073/pnas.2413302121.
Link: https://www.pnas.org/doi/10.1073/pnas.2413302121
Disclaimer: The news stories shared on this site are used as a way to inform our members and followers of updates and relevant information happening in Haematology. The BSH does not endorse the content of news items from external sources, and is not in a position to verify the findings, accuracy or the source of any studies mentioned. Any medical or drugs information is provided as an information resource only, and is not to be relied on for any diagnostic or treatment purposes.
News service provided by Englemed News.