| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
CANCER STEM CELLS |
aDepartment of Hematology, Azienda Ospedaliera-Universitaria Careggi, University of Florence, Florence, Italy;
bDepartment of Biomedical Sciences, Biological Chemistry Section, University of Modena and Reggio Emilia, Modena, Italy;
cINSERM U602, University Paris 11, Institut André Lwoff, Villejuif Cedex, France;
dUnit of Clinical Epidemiology, IRCCS Policlinico S. Matteo, Pavia, Italy;
eDepartment of Hematology, Oncology and Molecular Medicine, Istituto Superiore Sanità, Rome, Italy, and Department of Pathology, University of Illinois at Chicago, Illinois, USA, on behalf of the MPD Research Consortium
Key Words. Idiopathic myelofibrosis • CD34+ cells • Gene expression profiling • WT1 • JAK2V617F mutation
Correspondence: Alessandro M. Vannucchi, M.D., Department of Hematology, Azienda Ospedaliera-Universitaria Careggi, University of Florence, 50134 Florence, Italy. Telephone: +39.055.7947-688; Fax: +39.055.7947-688; e-mail: amvannucchi{at}unifi.it
Received June 8, 2006;
accepted for publication September 14, 2006.
First published online in STEM CELLS EXPRESS September 21, 2006.
This study was aimed at the characterization of a gene expression signature of the pluripotent hematopoietic CD34+ stem cell in idiopathic myelofibrosis (IM), which would eventually provide novel pathogenetic insights and/or diagnostic/prognostic information. Aberrantly regulated genes were revealed by transcriptome comparative microarray analysis of normal and IM CD34+ cells; selected genes were also assayed in granulocytes. One-hundred seventy four differentially expressed genes were identified and in part validated by quantitative polymerase chain reaction. Altered gene expression was corroborated by the detection of abnormally high CD9 or CD164, and low CXCR4, membrane protein expression in IM CD34+ cells. According to class prediction analysis, a set of eight genes (CD9, GAS2, DLK1, CDH1, WT1, NFE2, HMGA2, and CXCR4) properly recognized IM from normal CD34+ cells. These genes were aberrantly regulated also in IM granulocytes that could be reliably differentiated from control polycythemia vera and essential thrombocythemia granulocytes in 100% and 81% of cases, respectively. Abnormal expression of HMGA2 and CXCR4 in IM granulocytes was dependent on the presence and the mutational status of JAK2V617F mutation. The expression levels of both CD9 and DLK1 were associated with the platelet count, whereas higher WT1 expression levels identified IM patients with more active disease, as revealed by elevated CD34+ cell count and higher severity score. In conclusion, molecular profiling of IM CD34+ cells uncovered a limited number of genes with altered expression that, beyond their putative role in disease pathogenesis, are associated with patients' clinical characteristics and may have potential prognostic application.
This article has been cited by other articles:
|
|
 |
|
  H. Bruchova, M. Merkerova, and J. T. Prchal Aberrant expression of microRNA in polycythemia vera Haematologica, July 1, 2008; 93(7): 1009 - 1016. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Wernig, J. R. Gonneville, B. J. Crowley, M. S. Rodrigues, M. M. Reddy, H. E. Hudon, C. Walz, A. Reiter, K. Podar, Y. Royer, et al. The Jak2V617F oncogene associated with myeloproliferative diseases requires a functional FERM domain for transformation and for expression of the Myc and Pim proto-oncogenes Blood, April 1, 2008; 111(7): 3751 - 3759. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Tefferi Primary myelofibrosis and its paraneoplastic stromal effects Haematologica, May 1, 2007; 92(5): 577 - 579. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| STEM CELLS | THE ONCOLOGIST | CME | ALPHAMED PRESS JOURNALS |
