HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Caceres-Cortes, J.R. Articles by Hoang, T. Search for Related Content PubMed PubMed Citation Articles by Caceres-Cortes, J.R. Articles by Hoang, T.

Steel Factor Sustains SCL Expression and the Survival of Purified CD34⁺ Bone Marrow Cells in the Absence of Detectable Cell Differentiation

^a Laboratory of Hemopoiesis and Leukemia and
^b Clinical Research Institute of Montreal, Montreal, Quebec, Canada;
^c Research Unit in Cell Differentiation and Cancer, Faculty of Professional Studies-UNAM, FES-Zaragoza, UNAM, Mexico;
^d PROCREA BioSciences Inc., Institut de Recherches en Biotechnologie, Montreal, Quebec, Canada; the Departments of
^e Pharmacology and
^f Biochemistry, and the
^g Program of Molecular Biology, University of Montreal, Montreal, Quebec, Canada

Key Words. Apoptosis • Hemopoietic growth factor • Steel • Transcription factor SCL/tal-1 • Differentiation

Julio R. Caceres-Cortes, Ph.D., Research Unit in Cell Differentiation and Cancer, FES-Zaragoza-UNAM, J.C. Bonilla 66 Col. Ejercito de Oriente, Apdo Postal 9-020, Mexico D.F. CP 15000. Telephone: 525-773-4108; Fax: 525-773-4108; e-mail: cortesj{at}servidor.unam.mx

CD34⁺ cells express the basic helix-loop-helix transcription factor SCL, which is essential for blood cell formation in vivo. In addition, their survival is critically dependent on hemopoietic growth factors. We therefore compared the effects of Steel factor (SF) and GM-CSF on the survival, proliferation, and differentiation of primary human CD34⁺ cells, as well as the role of SCL during these processes. GM-CSF suppresses apoptosis in CD34⁺ cells, which proliferate and differentiate into mature granulocytic and monocytic cells (CD34^–CD13⁺) and loose SCL expression. In contrast, SF suppresses apoptosis without a significant increase in cell numbers, and the cells remain CD34⁺ and SCL⁺ with a blast-like morphology. Examination of apoptosis by the terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling (TUNEL) reaction and of the cell cycle status indicated that SF is both a survival factor and a mitogenic factor for CD34⁺ cells. There was, however, constant cell death in a fraction of the population, which could be rescued by GM-CSF. Co-addition of SF and GM-CSF prevents the downregulation of SCL observed in the presence of GM-CSF by itself, allows for prolonged survival and expansion of CD34⁺ cells in culture, inhibits monocytic differentiation and impairs granulocytic differentiation. Finally, exposure to an antisense SCL but not a control oligonucleotide decreases SCL protein levels and prevents the suppression of apoptosis by SF without affecting GM-CSF-dependent cell survival. These observations suggest that the hemopoietic transcription factor SCL regulates the survival of CD34⁺ cells in response to SF.

This article has been cited by other articles:

				E. Ravet, D. Reynaud, M. Titeux, B. Izac, S. Fichelson, P.-H. Romeo, A. Dubart-Kupperschmitt, and F. Pflumio Characterization of DNA-binding-dependent and -independent functions of SCL/TAL1 during human erythropoiesis Blood, May 1, 2004; 103(9): 3326 - 3335. [Abstract] [Full Text] [PDF]