LY86, LRG1 and PDE9A genes overexpression in umbilical cord blood hematopoietic stem progenitor cells by acute myeloid leukemia (M3) microvesicles

急性髓系白血病(M3)微囊泡导致脐带血造血干细胞祖细胞中LY86、LRG1和PDE9A基因过表达

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Abstract

BACKGROUND: Microvesicles as a new device of cell-cell communication are potentially able to induce some phenotypes and genotypes of an origin cell in a target cell. We evaluate the role of leukemia microvesicles on the leukemia stem cells (LSCs)-specific genes expression in healthy hematopoietic stem progenitor cells (HSPCs). METHODS: HL-60 and NB-4 cell lines were selected for microvesicles isolation by ultracentrifugation. Healthy HSPCs were obtained by magnetic association cell sorting (MACS) and CD-34 micro-beads from umbilical cord blood samples and then, were treated with 20 and 40 μg/ml leukemia microvesicles for 10 days, respectively. LY86, LRG1 and PDE9A genes expression as LSC specific genes were analyzed by QRT-PCR. Surface CD-34 antigen as stemness marker was measured by flow cytometry technique. RESULTS: Healthy HSPCs showed a significant increase in LSC specific genes expression after treatment with both 20 and 40 μg/ml leukemia microvesicles at day 10. All studied groups showed more than 70% surface CD-34 antigen at the last day of experiment which proved HSPCs stemness. CONCLUSION: Our results suggest that healthy HSPCs can be transformed genetically by leukemia microvesicles to over express LSC specific genes. This may be further evidence of leukemia-like transformation by leukemia microvesicles.

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