Phagocytosis checkpoints on hematopoietic stem cells in patients with myelodysplastic syndromes

Background The myelodysplastic syndrome (MDS) is a high-risk hemocytopenia easily converted to acute myeloid leukemia. CD47 plays an important role in regulating phagocytosis, and its role in the pathogenesis of MDS is unclear. Methods CD47 and PI3K/AKT/mTOR on CD34(+)CD38(-) cells were detected by flow cytometry. NF-kappa B, PI3K, AKT, PTEN, and mTOR mRNA overexpressed in CD34(+)CD38(-)CD47(+) cells were performed by real-time quantitative transcriptase-polymerase chain reaction. Phagocytic capacity of macrophages was measured with carboxyfluorescein succinimidyl ester and fluorescent microspheres. Sorted CD34(+)CD38(-)CD47(+) cells were injected into NOD-Prkdc(scid) Il2rg(null) mice. Results The expression of CD47 on CD34(+)CD38(-) cells of the patients in high-risk MDS based on IPSS-R/WPSS score was higher than that in low-risk MDS and controls. The signaling pathway of PI3K/AKT/mTOR is active in CD34(+)CD38(-)CD47(+) cells of MDS patients. CD47 overexpressing CD34(+)CD38(-) cells has antiphagocytosis. CD47 overexpressing leukemia stem cell (LSC) -transplanted mice has a short survival time. The macrophages originated from MDS might elicit a pro-tumor response in MDS by inhibiting phagocytosis. Conclusions Phagocytosis checkpoints are impaired in MDS. High expression of CD47 on CD34+CD38(-) cells indicates poor clinical prognosis in MDS.

Automated summary

Results indicate that high expression of CD47 on CD34(+)CD38(-) cells in high-risk MDS patients is associated with poor clinical prognosis. The PI3K/AKT/mTOR signaling pathway is active in CD34(+)CD38(-)CD47(+) cells of MDS patients, affecting phagocytosis of macrophages. Overexpression of CD47 may lead to anti-phagocytosis and decreased survival time in leukemia stem cell-transplanted mice.