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Evidence against a direct cytotoxic effect of alpha interferon and zidovudine in HTLV-I associated adult T cell leukemia/lymphoma.

Abstract：

:The combination of the anti-viral agents, zidovudine (AZT) and interferon-alpha (IFN), is a potent treatment of HTLV-I-associated adult T cell leukemia/lymphoma (ATL). In this study we investigate the possible mechanism of action of this combination by examining several cellular parameters including cell proliferation, cell cycle distribution and apoptosis. The ATL-derived T cell lines HuT-102 and MT-2 served as models. HTLV-I negative T cell lines (CEM and Jurkat) were used as controls. No significant modification of cell growth was observed except at suprapharmacological doses of AZT and IFN. Moreover, these effects were less pronounced in HTLV-I-infected cell lines compared to control cell lines. AZT and IFN treatment did not induce any significant modification of the expression of bcl-2 and p53. Interestingly no in vitro cytotoxic effect of AZT/IFN combination was observed on fresh leukemic cells derived from an acute ATL patient at diagnosis despite achievement of in vivo complete remission using the same therapy. These results suggest that the therapeutic effect of AZT and IFN is not through a direct cytotoxic effect of these drugs on the leukemic cells.

journal_name

Leukemia

journal_title

Leukemia

authors

Bazarbachi A,Nasr R,El-Sabban ME,Mahé A,Mahieux R,Gessain A,Darwiche N,Dbaibo G,Kersual J,Zermati Y,Dianoux L,Chelbi-Alix MK,de Thé H,Hermine O

doi

10.1038/sj.leu.2401742

subject

Has Abstract

pub_date

2000-04-01 00:00:00

pages

716-21

issue

4

eissn

0887-6924

issn

1476-5551

journal_volume

14

pub_type

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