Over expression of ubiquitin‐conjugating enzyme E2O in bone marrow mesenchymal stromal cells partially attenuates acute myeloid leukaemia progression. (8th November 2022)

• Record Type: Journal Article
• Authors: Tian, Chen; Chen, Zehui; Wang, Lina; Si, Junqi; Kang, Junnan; Li, Yueyang; Zheng, Yaxin; Gao, Yanan; Nuermaimaiti, Rexidan; You, M. James; Zheng, Guoguang
• Is Part Of: British journal of haematology. Volume 200:Number 4(2023)
• Page Start: 476
• Page End: 488
• Publication Date: 2022-11-08
• Subjects: acute myeloid leukaemia -- bone marrow mesenchymal stromal cells -- Leukaemia microenvironment -- NF‐κB pathway -- UBE2O; Hematology -- Periodicals; Blood -- Diseases -- Periodicals; 616.15
• DOI: 10.1111/bjh.18541
• Languages: English
• ISSNs: 0007-1048

Abstract

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