Thrombopoietin increases susceptibility for EVI1 + KMT2A-MLLT3-driven AML expressing stem cell genes linked to poor outcome.

ABSTRACT: To address the cellular origin of ecotropic virus integration site 1 (EVI1)-expressing aggressive KMT2A-rearranged acute myeloid leukaemia (AML) we integrate an Evi1-GFP reporter allele in the inducible iKMT2A-MLLT3 mouse model. We observe that a single injection of thrombopoietin (TPO) selectively increases the number of cycling Evi1⁺ haematopoietic stem cells (HSC) and accelerates AML initiation. Comparison of mouse Evi1⁺ KMT2-MLLT3⁺ AML originating from TPO-stimulated HSC with human EVI1⁺AML reveals higher expression of HSC genes including IL12Rβ2 and INPP4B linked to poor disease outcome of patients of four large AML cohorts. Knockdown experiments show exclusive MECOM-dependency of human EVI1^high KMT2A-rearranged OCI-AML4 cells whi

SUBMITTER: Chatel-Soulet HE 

PROVIDER: S-EPMC12830621 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature