Exosomes shed by acute myeloid leukemia (AML) cells carry microRNAs that directly impair hematopoiesis, according to preclinical research published in Science Signaling.
Previous research suggested that AML exosomes can suppress residual hematopoietic stem and progenitor cell (HSPC) function indirectly through stromal reprogramming of niche retention factors.
The new study indicates that AML exosomes can block hematopoiesis by delivering microRNAs that directly suppress blood production when taken up by HSPCs.
Noah Hornick, of Oregon Health & Science University in Portland, and his colleagues conducted this study, isolating exosomes from cultures of human AML cells and from the plasma of mice with AML.
The researchers found these exosomes were enriched in 2 microRNAs—miR-150 and miR-155.
When cultured with HSPCs, the exosomes suppressed the expression of the transcription factor c-MYB, which is involved in HSPC proliferation and differentiation.
Blocking the function of miR-155 prevented AML cells or their exosomes from reducing c-MYB abundance and inhibiting the proliferation of cultured HSPCs.
Using a method called RISC-Trap, the researchers identified other targets of microRNAs in AML exosomes, from which they predicted protein networks that could be disrupted in cells taking up the exosomes.
The team said this study suggests that interfering with exosome-delivered microRNAs in the bone marrow or restoring the abundance of their targets may enhance AML patients’ ability to produce healthy blood cells.
