AML-derived extracellular vesicles negatively regulate stem cell pool size: A step toward bone marrow failure

Bahrampour Shahrokh; Farsani Mehdi Allahbakhshian; Gharehbaghian Ahmad; Feizi Fatemeh; Mohammadi Mohammad Hossein

doi:10.1016/j.retram.2022.103375

AML-derived extracellular vesicles negatively regulate stem cell pool size: A step toward bone marrow failure

Curr Res Transl Med. 2023 Jan-Mar;71(1):103375. doi: 10.1016/j.retram.2022.103375. Epub 2022 Nov 30.

Authors

Bahrampour Shahrokh¹, Farsani Mehdi Allahbakhshian², Gharehbaghian Ahmad¹, Feizi Fatemeh¹, Mohammadi Mohammad Hossein³

Affiliations

¹ Laboratory Hematology and Blood Banking, School of Allied Medical Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
² Laboratory Hematology and Blood Banking, School of Allied Medical Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran; HSCT Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
³ Laboratory Hematology and Blood Banking, School of Allied Medical Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran; HSCT Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: drmohammadi@sbmu.ac.ir.

PMID: 36508911
DOI: 10.1016/j.retram.2022.103375

Abstract

Purpose of the study: Long-term repopulating hematopoietic stem cells (LTR-HSCs) have been previously shown to reside in close proximity to osteoblasts, where they take shelter in the bone marrow (BM) microenvironment against cytotoxic and apoptotic stimuli. Nevertheless, the function of the HSC niche is believed to undergo an adaptive evolutionary modification during leukemogenesis. Recent studies have demonstrated that leukemic clones can impact BM homing through extracellular vesicle (EV) secretion. However, the exact mechanism driving BM conversion is still unclear. In the present study, the human osteoblast cell line (MG-63) were subjected to various concentration of sera-derived EVs of patients with acute myeloid leukemia (AML) and healthy volunteers to assess if they are associated strongly enough to alter the expression pattern of cross-talk molecules involved in niche interactions.

Method: To gain a brief insight into the EVs secretion criteria, we first conducted a comparative analysis of sera-derived EVs by dynamic light scattering (DLS), transmission electron microscopy (TEM), and Bradford assay. After incubating MG-63 cell lines with increasing concentrations of the EVs, Trypan-blue and microculture tetrazolium test (MTT) assays were used to evaluate the cell survival, logarithmic growth, and metabolic activity. Finally, the expression levels of OPN, ANGPT-1, and JAG-1 transcripts were evaluated through the qRT-PCR technique.

Results: Here, we report that AML-derived EVs can affect the viability, cell growth, and metabolic activity of the human osteoblasts cell line (MG-63) compared to those that received healthy-derived EVs. We also found that leukemic EVs tend to induce overexpression of OPN but reduce the expression of ANGPT-1 and JAG-1 genes in the osteoblast transcriptome, which may provide a potential context imposing selective suppression of HSC pool size.

Conclusion: These findings extend the general concept of a novel mechanism in which leukemic EVs would make it possible to create a specialized pre-metastatic microenvironment in the interest of tumor expansion, allowing leukemic clones to overcome their HSCs counterparts.

Keywords: Acute myeloid leukemia; Cell adhesion molecule; Extracellular vesicles; Hematopoiesis; Osteoblast.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Bone Marrow / pathology
Bone Marrow Failure Disorders / metabolism
Bone Marrow Failure Disorders / pathology
Extracellular Vesicles*
Hematopoietic Stem Cells
Humans
Leukemia, Myeloid, Acute* / genetics
Leukemia, Myeloid, Acute* / pathology
Tumor Microenvironment