Search

Your search keyword '"Hall, William W."' showing total 8 results
Start Over Author "Hall, William W." Journal blood
8 results on '"Hall, William W."'

7. Inhibition of the SDF-1α–CXCR4 axis by the CXCR4 antagonist AMD3100 suppresses the migration of cultured cells from ATL patients and murine lymphoblastoid cells from HTLV-I Taxtransgenic mice

Author

Kawaguchi, Akira, Orba, Yasuko, Kimura, Takashi, Iha, Hidekatsu, Ogata, Masao, Tsuji, Takahiro, Ainai, Akira, Sata, Tetsutaro, Okamoto, Takashi, Hall, William W., Sawa, Hirofumi, and Hasegawa, Hideki

Abstract

Adult T-cell leukemia (ATL) is a T-cell malignancy caused by human T lymphotropic virus type I, and presents as an aggressive leukemia with characteristic widespread leukemic cell infiltration into visceral organs and skin. The molecular mechanisms associated with leukemic cell infiltration are poorly understood. We have used mouse models of ATL to investigate the role of chemokines in this process. Transfer of splenic lymphomatous cells from transgenic to SCID mice reproduces a leukemia and lymphoma that is histologically identical to human disease. It could be shown that lymphomatous cells exhibit specific chemotactic activity in response to stromal cell–derived factor-1α (SDF-1α). Lymphomatous cells exhibited surface expression of CXCR4, the specific receptor of SDF-1α. AMD3100, a CXCR4 antagonist, was found to inhibit both SDF-1α–induced migration and phosphorylation of extracellular signal-related kinase 1/2. Investigation of cultured cells from human ATL patients revealed identical findings. Using the SCID mouse model, it could be demonstrated that AMD3100 inhibited infiltration of lymphomatous cells into liver and lung tissues in vivo. These results demonstrate the involvement of the SDF-1α/CXCR4 interaction as one mechanism of leukemic cell migration and this may provide a novel target as part of combination therapy for ATL.

Published
2009
Full Text
View/download PDF

8. Preclinical efficacy of the synthetic retinoid ST1926 for treating adult T-cell leukemia/lymphoma.

Author

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

Subjects
*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
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results