Targeting of DNMT3A hotspot mutations in Clonal Hematopoiesis and Acute Myeloid Leukemia

Somatic mutations in DNA Methyltransferase 3A (DNMT3A) with a hotspot in exon 23 at Arginine 882 (DNMT3AR882mut) are the most frequent single mutations in clonal hematopoiesis. Here we analyze the expression of genes and endogenous retrovirus (ERV) sequences in a murine model carrying human DNMT3A-R882H mutation in one allele of the endogenous DNMT3A with respect to normal condition and azacitidine treatment. Lineage- Sca1+ Kit + (LSK) sorted bone marrow cells from WT DNMT3A and mice habouring a human DNMT3A R882H mutant allele in the endogenous locus were subject to transcriptomic sequencing under normal and azazytidine treatment condition. Expression levels of genes as well as repetitive elements were investigated.