Adult T-cell leukemia/lymphoma (ATL) is an aggressive neoplasm caused by human T-cell leukemia virus type 1 (HTLV-1). The HTLV-1 oncoprotein Tax plays an important role in ATL pathogenesis. ATL ...carries a poor prognosis due to chemotherapy resistance, stressing the need for alternative therapies. Here, we investigate the preclinical efficacy of the synthetic retinoid ST1926 in ATL and peripheral T-cell lymphomas. Clinically achievable concentrations of ST1926 induced a dramatic inhibition of cell proliferation in malignant T-cell lines and primary ATL cells with minimal effect on resting or activated normal lymphocytes. ST1926 induced apoptosis, DNA damage, and upregulation of p53 proteins in malignant T cells, whereas it caused an early downregulation of Tax proteins in HTLV-1–positive cells. In murine ATL, oral treatment with ST1926 prolonged survival and reduced leukemia cell infiltration, white blood cell counts, and spleen mass. In spleens of ST1926-treated animals, p53 and p21 proteins were upregulated, poly (ADP-ribose) polymerase was cleaved, and Tax transcripts were reduced. These results highlight the promising use of ST1926 as a targeted therapy for ATL.
•The synthetic retinoid ST1926 induces apoptosis of ATL cells and prolongs survival of ATL mice.•At the molecular level, ST1926 causes early DNA damage, upregulates p53, and downregulates Tax expression.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A top Kuwaiti official said the oil-rich country will be a “prudent” borrower after raising $8 billion in its first international bond sale at rates lower than other Gulf Arab states seeking to plug ...budget deficits. Citigroup Inc., HSBC Holdings Plc, JPMorgan Chase & Co., Deutsche Bank AG, NBK Capital and Standard Chartered Plc managed the sale. To read more About Kuwait’s 2017-2018 budget plans, click here Al-Saleh, who is also the finance minister and chairman of the country’s sovereign wealth fund, said the bond sale “covers the bulk of our funding needs from the international market in 2017.”
