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Down-regulation of signal transducer and activator of transcription 3 improves human acute myeloid leukemia-derived dendritic cell function.

ABSTRACT: 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.

SUBMITTER: Brady MT

PROVIDER: S-EPMC3672324 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Down-regulation of signal transducer and activator of transcription 3 improves human acute myeloid leukemia-derived dendritic cell function.

Brady Michael T MT Miller Austin A Sait Sheila N SN Ford Laurie A LA Minderman Hans H Wang Eunice S ES Lee Kelvin P KP Baumann Heinz H Wetzler Meir M

Leukemia research 20130428 7

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 ...[more]

PMID: 23628554

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