Mutations occur in CD34⁺ progenitors, leading to oncogenic transformation; AML cells reprogram the MSC transcriptome and secretome through CX43-mediated cell contact and create an onco-niche (AML-MSC). Dual targeting of MSCs with calcium channel (CaVI.2) blocker lercanidipine and AML cells with standard chemotherapeutic Ara-C reduces leukemia burden and restores healthy features of MSCs during the remission (R-MSC). Figure created with BioRender.com.