Phagocytosis checkpoints on hematopoietic stem cells in patients with myelodysplastic syndromes

Abstract

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-κB, 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.

Keywords: CD47; myelodysplastic syndromes; phagocytosis.