Yazarlar : El Hajj H, Khalil B, Ghandour B et al

Yayın : Blood

Yayın Yılı : 2014

Pubmed Linki : http://www.docguide.com/pre-clinical-efficacy-synthetic-retinoid-st1926-treating-adult-t-cell-leukemia-lymphoma?tsid=5

Konu : Lenfoma

Literatür İçeriği :  Adult T cell leukemia/lymphoma (ATL) is an aggressive neoplasm caused by the 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, while 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, PARP was cleaved while Tax transcripts were reduced. These results highlight the promising use of ST1926 as a targeted therapy for ATL.

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