1. Preclinical efficacy of the synthetic retinoid ST1926 for treating adult T-cell leukemia/lymphoma.
- Author
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Hajj, Hiba El, Khalil, Bariaa, Ghandour, Botheina, Nasr, Rihab, Shahine, Sharif, Ghantous, Akram, Abdel-Samad, Rana, Sinjab, Ansam, Hasegawa, Hideki, Jabbour, Mark, Hall, William W., Zaatari, Ghazi, Dbaibo, Ghassan, Pisano, Claudio, Bazarbachi, Ali, and Darwiche, Nadine
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LYMPHOCYTES , *T cells , *LYMPHOMAS , *PROGNOSIS , *RETINOID X receptors - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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