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J Exp Med. 2010 Dec 20;207(13):2785-92. doi: 10.1084/jem.20101095. Epub 2010 Dec 6.

Therapy-induced selective loss of leukemia-initiating activity in murine adult T cell leukemia.

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  • 1Department of Internal Medicine, Faculty of Medicine, American University of Beirut, Beirut 1107 2020, Lebanon.

Abstract

Chronic HTLV-I (human T cell lymphotropic virus type I) infection may cause adult T cell leukemia/lymphoma (ATL), a disease with dismal long-term prognosis. The HTLV-I transactivator, Tax, initiates ATL in transgenic mice. In this study, we demonstrate that an As(2)O(3) and IFN-α combination, known to trigger Tax proteolysis, cures Tax-driven ATL in mice. Unexpectedly, this combination therapy abrogated initial leukemia engraftment into secondary recipients, whereas the primary tumor bulk still grew in the primary hosts, only to ultimately abate later on. This loss of initial transplantability required proteasome function. A similar regimen recently yielded unprecedented disease control in human ATL. Our demonstration that this drug combination targeting Tax stability abrogates tumor cell immortality but not short-term growth may foretell a favorable long-term efficiency of this regimen in patients.

PMID:
21135137
[PubMed - indexed for MEDLINE]
PMCID:
PMC3005222
Free PMC Article

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