Leukemia microvesicles affect healthy hematopoietic stem cells

Abstract

Microvesicles are released by different cell types and shuttle mRNAs and microRNAs which have the possibility to transfer genetic information to a target cell and alter its function. Acute myeloid leukemia is a malignant disorder, and leukemic cells occupy all the bone marrow microenvironment. In this study, we investigate the effect of leukemia microvesicles on healthy umbilical cord blood hematopoietic stem cells to find evidence of cell information transferring. Leukemia microvesicles were isolated from acute myeloid leukemia patients and were co-incubated with healthy hematopoietic stem cells. After 7 days, cell count, hematopoietic stem cell-specific cluster of differentiation (CD) markers, colony-forming unit assay, and some microRNA gene expressions were assessed. Data showed a higher number of hematopoietic stem cells after being treated with leukemia microvesicles compared with control (treated with no microvesicles) and normal (treated with normal microvesicles) groups. Also, increased levels of microRNA-21 and microRNA-29a genes were observed in this group, while colony-forming ability was still maintained and high ranges of CD34 + , CD34 + CD38 − , CD90 + , and CD117 + phenotypes were observed as stemness signs. Our results suggest that leukemia microvesicles are able to induce some effects on healthy hematopoietic stem cells such as promoting cell survival and some microRNAs deregulation, while stemness is maintained.

Microvesicles released from multiple myeloma cells are equipped with ectoenzymes belonging to canonical and non-canonical adenosinergic pathways and produce adenosine from ATP and NAD+

“…The underlying mechanism(s) are various, and sometimes contradictory. In fact, MVs are capable of stimulating tumor cell proliferation, 24 inducing angiogenesis, 20,28 suppressing normal cell development, 21,29,30 modulating tumor/microenvironment interactions 31 and inhibiting anti-tumor immune response. 17,22,32 The role of MVs in the context of human MM is now being investigated.…”

Extracellular vesicles in the hematopoietic microenvironment

“… 14 On the other hand, one study showed that AML EVs increased the number of HSCs by enhancing their survival while retaining their clonogenicity and stemness with no change in the hematopoietic CD34 + , CD34 + CD38 − , CD90 + , and CD117 + phenotypes. 67 Illustrating one of the key challenges in understanding HSPC regulation by EVs, neither of the two latter studies identified the specific EV component responsible. We and others previously showed that EVs released by steady-state or reprogrammed malignant stroma carry cytokines.…”

Mesenchymal stromal cell‐derived extracellular vesicles as cell‐free biologics for the ex vivo expansion of hematopoietic stem cells

“…A similar effect of leukemic BM cell‐derived MVs was seen on healthy UCB‐derived HSCs. Although increased levels of the oncomir miRNA‐21 and miRNA‐29a genes were observed in the treated HSCs, the colony‐forming ability was retained and high ranges of CD34 + , CD34 + CD38 − , CD90 + , and CD117 + phenotypes were perceived as signs of stemness (Razmkhah et al, 2017).…”