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

نویسندگان

  • 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
چکیده

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.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Gnidilatimonoein from Daphne mucronata induced differentiation and apoptosis in leukemia cell lines

Among various treatments, plants play a crucial role in cancer chemotherapy. Base on literature data, different species of the thymeleaeceae family have been found to be good sources for anticancer agents. Therefore, our laboratory has initiated a research project on evaluating the anticancer properties of the Iranian medical plant, Daphne mucronata (Thymeleaeceae). Gnidilatimonoein is a new di...

متن کامل

Gnidilatimonoein from Daphne mucronata induced differentiation and apoptosis in leukemia cell lines

Among various treatments, plants play a crucial role in cancer chemotherapy. Base on literature data, different species of the thymeleaeceae family have been found to be good sources for anticancer agents. Therefore, our laboratory has initiated a research project on evaluating the anticancer properties of the Iranian medical plant, Daphne mucronata (Thymeleaeceae). Gnidilatimonoein is a new di...

متن کامل

Diffuse normolipemic plane Xanthoma in adult T-cell lymphoma/leukemia: A case report

Diffuse normolipemic plane xanthoma is a rare disorder often seen as a para-neoplastic manifestation accompanied with gammopathies and hematologic disorders. In this report, a 44-year-old man is presented who was referred to us due to developing erythematous papules on the hands and yellow patches on different parts of the body. Based on cell blood count, peripheral blood smear and positive ant...

متن کامل

Profiles of MMP-2 Expression in Jurkat, Molt-4 and U937 Cells

Background: Leukemia is a malignant proliferative disorder of the hematopoietic cells. The important role of angiogenesis in leukemia has been reported by several studies. Matrix metalloproteinases (MMPs) are a large group of endopeptidases which degredate the extracellular matrix and play an important role in angiogenesis. Objective: The present study was conducted to evaluate the patterns of ...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 207  شماره 

صفحات  -

تاریخ انتشار 2010