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

• DOI: 10.1084/jem.20101095
• Publication Date: 2010-12-07T06:20:13Z
• Authors: Hiba El Hajj; Marwan El-Sabban; Hideki Hasegawa; Ghazi Zaatari; Julien Ablain; Shahrazad T. Saab; Anne Janin; Rami Mahfouz; Rihab Nasr; Youmna Kfoury; Christophe Nicot; Olivier Hermine; William Hall; Hugues de Thé; Ali Bazarbachi
• Keywords: Adult T-cell leukemia/lymphoma

Chronic HTLV-I (human T cell lymphotropic virus type I) infection may cause adult leukemia/lymphoma (ATL), a disease with dismal long-term prognosis. The transactivator, Tax, initiates ATL in transgenic mice. In this study, we demonstrate that an As2O3 and IFN-α combination, known to trigger Tax proteolysis, cures Tax-driven Unexpectedly, combination therapy abrogated initial leukemia engraftment into secondary recipients, whereas the primary tumor bulk still grew hosts, only ultimately abate later on. This loss of transplantability required proteasome function. A similar regimen recently yielded unprecedented control human ATL. Our demonstration drug targeting stability abrogates immortality but not short-term growth foretell favorable efficiency patients.