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Sotic cell gene mutations are a key determinant of prognosis in patients with bone marrow proplation abnormal syndrome (MDS) and secondary acute myeloid leukemia (SAML).
especially the TP53 mutation, which represents a different molecular queue, and patients with TP53 mutations tend to have poor prognosis.
, the exact mechanism of these adverse outcomes has not been clarified.
, Sallman and others described the immunological characteristics and changes of malignant cloning in the immunomic micro-environment of patients with TP53 mutations and wild MDS and SAML.
notably, PD-L1 expression increased significantly in hematopoietic stem cells in patients with TP53 mutants, which was associated with a significant reduction in myC upslation and myC's negative regulatory factor miR-34a (p53 transcription target).
addition, the number of OX40-plus cytotoxic T-cells and auxiliary T-cells immersed in the bone marrow of patients with the TP53 mutant type decreased significantly, as did the number of ICOS plus and 4-1BB plus NK cells.
in TP53 mutant cases, high immunosuppressive regulatory T-cells (e.g. ICOS High/PD-1neg) and MDSCs (PD-1low) amplification.
, a higher proportion of bone marrow-soaked ICOS High/PD-1neg Tregs is a very significant independent predictor of overall survival.
To sum up, this study shows that the microencupypes of TP53 mutant MDS and SAML have immune privileges and avoidance diastics, which may be the main driver of patients' poor prognostication, and suggest that immunomodating therapy strategies may provide benefits to this sub-group of patients.
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