Over expression of ubiquitin‐conjugating enzyme E2O in bone marrow mesenchymal stromal cells partially attenuates acute myeloid leukaemia progression

• DOI: 10.1111/bjh.18541
• Publication Date: 2022-11-08T09:36:06Z
• Authors: Chen Tian; Zehui Chen; Lina Wang; Junqi Si; Junnan Kang; Yueyang Li; Yaxin Zheng; Yanan Gao; Rexidan Nuermaimaiti; M. James You; Guoguang Zheng
• Keywords: 0301 basic medicine; Mice; Leukemia, Myeloid, Acute; 03 medical and health sciences; Bone Marrow; Ubiquitin-Conjugating Enzymes; NF-kappa B; Tumor Microenvironment; Animals; Bone Marrow Cells; Mesenchymal Stem Cells; 3. Good health

Summary Bone marrow mesenchymal stromal cells (BM‐MSCs) are implicated in the pathogenesis of acute myeloid leukaemia (AML). However, due to high heterogeneity AML mechanism underlying cross‐talk between MSCs and is not well understood. We found that mixed‐lineage leukaemia‐AF9 (MLL‐AF9)‐induced mice‐derived had higher proliferative viability compared wild‐type with ubiquitin‐conjugating enzyme E2O ( Ube2o ) down‐regulation. After overexpression UBE2O AML‐derived MSCs, growth capacity was reduced nuclear factor kappa B subunit 1 (NF‐κB) pathway deactivation. In vitro co‐culture assay revealed UBE2O‐overexpression suppressed proliferation promoted apoptosis by direct contact. vivo results burden overall survival mice prolonged, decreased dissemination BM, spleen, liver peripheral blood. Additionally, subcutaneous tumorigenesis tumour also group. conclusion, expressed at a low level MLL‐AF9‐induced MSCs. Overexpression their through NF‐κB deactivation, which resulted suppression. Our study provides theoretical basis for BM microenvironment‐based therapeutic strategy control disease progression.