Deguelin induced differentiation of mutated NPM1 acute myeloid leukemia in vivo and in vitro.

摘要: Nucleophosmin (NPM1), a restricted nucleolar localization protein, shuttles between the nucleus and cytoplasm. Mutated (Mt)-NPM1 which has aberrant cytoplasmic dislocation of nucleophosmin, occurs in approximately one-third acute myeloid leukemia cases. Deguelin, rotenoid isolated from several plant species, is strong antitumor agent. NOD/SCID mice xenografted with human Mt-NPM1 OCI/AML3 cell lines served as in-vivo models. Wright-Giemsa staining flow cytometry analysis were used for differentiation assays. Associated molecular events assessed by western blot histological analyses. Kaplan-Meier estimates to calculate survival. Deguelin toxicity was immunohistochemistry serum markers. Clinical samples differentiated analysis. induced downregulating protein levels, accompanied decrease SIRT1, p21, HDAC1 an increase CEBPβ granulocyte colony-stimulating factor receptor expression levels. A low-deguelin dose prolonged survival compared control group, there no apparent lesions brain, liver, heart, kidney vivo. In clinical samples, deguelin fresh blasts but not wild-type NPM1 protein. Taken together, these findings further provide new evidence that plays important role inducing vivo vitro. may be therapeutic target mutation.