Mitochondrial pro-apoptotic ARTS protein is lost in the majority of acute lymphoblastic leukemia patients

Ronit Elhasid, Dvora Sahar, Ayellet Merling, Yifat Zivony, Asaf Rotem, Miriam Ben-Arush, Shai Izraeli, Dani Bercovich, Sarit Larisch

Research output: Contribution to journalArticlepeer-review


Acquired resistance towards apoptosis is the hallmark of most if not all types of cancer. We have previously identified and characterized ARTS, a broadly expressed protein localized to mitochondria. ARTS was initially shown to mediate TGF-β induced apoptosis. Recently, we have found that high levels of ARTS induce apoptosis without additional pro-apoptotic stimuli. Further, ARTS promotes apoptosis in response to a wide variety of proapoptotic stimuli. Here, we report that the expression of ARTS is lost in all lymphoblasts of more than 70% of childhood acute lymphoblastic leukemia (ALL) patients. The loss of ARTS is specific, as the related non-apoptotic protein H5, bearing 83% identity to ARTS, is unaffected. During remission, ARTS expression is detected again in almost all patients. Two leukemic cell lines, ALL-1 and HL-60 lacking ARTS, were resistant to apoptotic induction by ara-C. Transfection of ARTS into these cells restored their ability to undergo apoptosis in response to this chemotherapeutic agent. We found that methylation process contributes to the loss of ARTS expression. We conclude that the loss of ARTS may provide a selective advantage for cells to escape apoptosis thereby contributing to their transformation to malignant lymphoblasts. We therefore propose that ARTS can fraction as a tumor suppressor protein in childhood ALL.

Original languageEnglish
Pages (from-to)5468-5475
Number of pages8
Issue number32
StatePublished - 15 Jul 2004
Externally publishedYes

Bibliographical note

Funding Information:
We wish to thank Hermann Steller for his help throughout this work and for thoughtful reading of the manuscript. We also thank Ziva Weissman for excellent technical assistance, Zvi Ben-Ishai from Rambam Medical Center, Haifa, Israel for his continuous support, David Barzilai and the Erna D Leir Foundation for Research of Degenerative Brain Diseases for their generous support. This work was supported by a grant from the Israel Cancer Association and a grant from the Israel Science Foundation.


  • ARTS
  • Apoptosis
  • Leukemia
  • Mitochandria

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research


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