In this issue of Blood, Sallman et al(1) show that myelodysplastic syndrome (MDS) and secondary acute myeloid leukemia (sAML) harboring a TP53 mutation (TP53(mut)) are characterized by immune checkpoint overexpression (programmed death ligand 1 [PD-L1]) at the stem cell level (see figure), which is mediated by dysregulation of the mir-34a/MYC circuit, reduced numbers of cytotoxic T cells, and expansion of myeloid-derived suppressor cells (MDSCs) and ICOShigh/PD-1(neg) regulatory T cells (Tregs). The latter independently correlated with adverse overall survival. The paucity of additional somatic mutations in TP53mut cases was also confirmed in this study, which indicates that this is a distinct molecular entity. MDS/sAML with TP53mut may be enriched with an immunosuppressive profile that could be the primary driver of the rather dismal prognosis found in this molecularly defined subset.

Natural born survivors: The inglorious TP53

Kordasti S.
Conceptualization
2020-01-01

Abstract

In this issue of Blood, Sallman et al(1) show that myelodysplastic syndrome (MDS) and secondary acute myeloid leukemia (sAML) harboring a TP53 mutation (TP53(mut)) are characterized by immune checkpoint overexpression (programmed death ligand 1 [PD-L1]) at the stem cell level (see figure), which is mediated by dysregulation of the mir-34a/MYC circuit, reduced numbers of cytotoxic T cells, and expansion of myeloid-derived suppressor cells (MDSCs) and ICOShigh/PD-1(neg) regulatory T cells (Tregs). The latter independently correlated with adverse overall survival. The paucity of additional somatic mutations in TP53mut cases was also confirmed in this study, which indicates that this is a distinct molecular entity. MDS/sAML with TP53mut may be enriched with an immunosuppressive profile that could be the primary driver of the rather dismal prognosis found in this molecularly defined subset.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11566/290419
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