nsc-74859 and Blast-Crisis

Signal transducer and activator of transcription (STAT) 3 inhibits dendritic cell (DC) differentiation and is constitutively activated in blasts of approximately half of AML patients. We investigated the correlation between STAT3 activity, DC maturation and the ability to stimulate T-cells in primary acute myeloid leukemia (AML)-derived DCs. STAT3 knock-down by shRNAmir increased the ability of AML-DCs to stimulate T-cells. Treatment of AML-DC with arsenic trioxide, but not AG490, JSI-124 or NSC-74859, led to a more mature phenotype and enhanced T-cell stimulation, while having minimal effect on normal DC. We conclude that AML-DCs have improved immunogenicity after reducing STAT3.

Topics: Aminosalicylic Acids; Antigen-Presenting Cells; Antineoplastic Agents; Arsenic Trioxide; Arsenicals; Benzenesulfonates; Blast Crisis; Blotting, Western; Dendritic Cells; Down-Regulation; Endocytosis; Enzyme-Linked Immunosorbent Assay; Humans; Immunophenotyping; In Situ Hybridization, Fluorescence; Leukemia, Myeloid, Acute; Lymphocyte Activation; Oxides; RNA, Small Interfering; Signal Transduction; STAT3 Transcription Factor; T-Lymphocytes; Tumor Cells, Cultured