Haematologica
HOME HELP FEEDBACK TABLE OF CONTENTS ARCHIVE SUBSCRIPTIONS
QUICK SEARCH:   [advanced]


     

Haematologica, Vol 92, Issue 3, 323-331 doi:10.3324/haematol.10541
Copyright © 2007 by Ferrata Storti Foundation
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Zheng, X.
Right arrow Articles by Ruthardt, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zheng, X.
Right arrow Articles by Ruthardt, M.
Related Collections
Right arrowRelated Article

Acute Promyelocytic Leukemia

Arsenic but not all-trans retinoic acid overcomes the aberrant stem cell capacity of PML/RAR{alpha}-positive leukemic stem cells

Xiaomin Zheng, Anita Seshire, Brigitte Rüster, Gesine Bug, Tim Beissert, Elena Puccetti, Dieter Hoelzer, Reinhard Henschler, Martin Ruthardt

From the Laboratory of Tumor Stem Cell Biology, Department of Hematology, J.W. Goethe University, Frankfurt, Germany (XZ, AS, GB, TB, EP, DH, MR); Department of Transfusion Medicine and Immunohematology, J.W. Goethe University, Frankfurt, Germany (BR, RH).

Correspondence: Martin Ruthardt, M.D., Med. Klinik II/Hämatologie, Klinikum der J.W. Goethe Universität Frankfurt, Theodor Stern Kai 7, 60590 Frankfurt, Germany. E-mail: ruthardt{at}em.uni-frankfurt.de

Background and Objectives: Stem cells play an important role in the pathogenesis and maintenance of most malignant tumors. Acute myeloid leukemia (AML) is a stem cell disease. The inefficient targeting of the leukemic stem cells (LSC) is considered responsible for relapse after the induction of complete hematologic remission (CR) in AML. Acute promyelocytic leukemia (APL) is a subtype of AML characterized by the t(15;17) translocation and expression of the PML/RAR{alpha} fusion protein. Treatment of APL with all-trans retinoic acid (ATRA) induces CR, but not molecular remission (CMR), because the fusion transcript remains detectable, followed by relapse within a few months. Arsenic induces high rates of CR and CMR followed by a long relapse-free survival (RFS). Here we compared the effects of ATRA and arsenic on PML/RAR{alpha}-positive stem cell compartments.

Design and Methods: As models for the PML/RAR{alpha}-positive LSC we used: (i) Sca1+/lin– murine HSC retro-virally transduced with PML/RAR{alpha}; (ii) LSC from mice with PML/RAR{alpha}-positive leukemia; (iii) the side population of the APL cell line NB4.

Results: In contrast to ATRA, arsenic abolishes the aberrant stem cell capacity of PML/RAR{alpha}-positive stem cells. Arsenic had no apparent influence on the proliferation of PML/RAR{alpha}-positive stem cells, whereas ATRA greatly increased the proliferation of these cells. Furthermore ATRA induces proliferation of APL-derived stem cells, whereas arsenic inhibits their growth.

Interpretations and Conclusions: Taken together our data suggest a relationship between the capacity of a compound to target the leukemia-initiating cell and its ability to induce long relapse-free survival. These data strongly support the importance of efficient LSC-targeting for the outcome of patients with leukemia.

Key words: acute promyelocytic leukemia, arsenic, all-trans retinoic acid, leukemic stem cell.


Related Article

Current treatment of acute promyelocytic leukemia
Francesco Lo-Coco, Emanuele Ammatuna, Miguel A. Sanz
Haematologica 2007 92: 289-291. [Full Text] [PDF]





HOME HELP FEEDBACK TABLE OF CONTENTS ARCHIVE SUBSCRIPTIONS
Copyright © 2007 by the Ferrata Storti Foundation.