Molecular Cancer Research Funding AM Call for Abstracts
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
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 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
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Jelinek, D. F.
Right arrow Articles by Kay, N. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jelinek, D. F.
Right arrow Articles by Kay, N. E.
Molecular Cancer Research 1:346-361 (2003)
© 2003 American Association for Cancer Research

Cancer Genes and Genomics

Identification of a Global Gene Expression Signature of B-Chronic Lymphocytic Leukemia1

Diane F. Jelinek1, Renee C. Tschumper1, Gustavo A. Stolovitzky4, Stephen J. Iturria2, Yuhai Tu4, Jorge Lepre4, Nigam Shah4 and Neil E. Kay3

1 Departments of Immunology, 2 Biostatistics, and 3 Internal Medicine, Mayo Graduate and Medical Schools, Mayo Clinic, Rochester, MN; and
4 IBM, T.J. Watson Research Center, Yorktown Heights, New York, NY

Requests for reprints: Diane F. Jelinek, Department of Immunology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905. Phone: (507) 284-5617; Fax: (507) 266-0981. E-mail: jelinek.diane{at}mayo.edu

B-chronic lymphocytic leukemia (B-CLL) is an adult-onset leukemia characterized by significant accumulation of apoptosis-resistant monoclonal B lymphocytes. In this study, we performed gene expression profiling on B cells obtained from 10 healthy age-matched individuals and CLL B cells from 38 B-CLL patients to identify key genetic differences between CLL and normal B cells. In addition, we leveraged recent independent studies to assess the reproducibility of our molecular B-CLL signature. We used a novel combination of several methods of data analysis including our own software and identified 70 previously unreported genes that differentiate leukemic cells from normal B cells, as well as confirmed recently reported B-CLL specific expression levels of an additional 10 genes. Importantly, many of these genes have previously been linked with other cancers, thus lending further support to their importance as candidate genes leading to B-CLL pathogenesis. We have also validated a subset of these genes using independent methodologies. Moreover, we show that our genes can be used to create a diagnostics signature that performs with perfect sensitivity and specificity in an independent cohort of 21 B-CLL and 20 normal subjects, thus strongly validating the informative nature of our set of genes. Finally, we identified a group of 31 genes that distinguish between low (Rai stage 0) and high (Rai stage 4) risk patients, suggesting that there may also be a gene expression signature that associates with disease progression.

Key Words: gene expression profiling • B-CLL • immunoglobulin mutation status




This article has been cited by other articles:


Home page
 Mol. Cell. Biol.Home page
R. J. Wozniak, S. Keles, J. J. Lugus, K. H. Young, M. E. Boyer, T. M. Tran, K. Choi, and E. H. Bresnick
Molecular Hallmarks of Endogenous Chromatin Complexes Containing Master Regulators of Hematopoiesis
Mol. Cell. Biol., November 1, 2008; 28(21): 6681 - 6694.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
T. L. Criswell, N. Dumont, J. V. Barnett, and C. L. Arteaga
Knockdown of the Transforming Growth Factor-{beta} Type III Receptor Impairs Motility and Invasion of Metastatic Cancer Cells
Cancer Res., September 15, 2008; 68(18): 7304 - 7312.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
V. Gattei, P. Bulian, M. I. Del Principe, A. Zucchetto, L. Maurillo, F. Buccisano, R. Bomben, M. Dal-Bo, F. Luciano, F. M. Rossi, et al.
Relevance of CD49d protein expression as overall survival and progressive disease prognosticator in chronic lymphocytic leukemia
Blood, January 15, 2008; 111(2): 865 - 873.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
A. D. Joshi, G. V. Hegde, J. D. Dickinson, A. K. Mittal, J. C. Lynch, J. D. Eudy, J. O. Armitage, P. J. Bierman, R. G. Bociek, M. P. Devetten, et al.
ATM, CTLA4, MNDA, and HEM1 in High versus Low CD38 Expressing B-Cell Chronic Lymphocytic Leukemia
Clin. Cancer Res., September 15, 2007; 13(18): 5295 - 5304.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Chem.Home page
P. Alvarez, P. Saenz, D. Arteta, A. Martinez, M. Pocovi, L. Simon, and P. Giraldo
Transcriptional Profiling of Hematologic Malignancies with a Low-Density DNA Microarray
Clin. Chem., February 1, 2007; 53(2): 259 - 267.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
W. J. Chng, R. F. Schop, T. Price-Troska, I. Ghobrial, N. Kay, D. F. Jelinek, M. A. Gertz, A. Dispenzieri, M. Lacy, R. A. Kyle, et al.
Gene-expression profiling of Waldenstrom macroglobulinemia reveals a phenotype more similar to chronic lymphocytic leukemia than multiple myeloma
Blood, October 15, 2006; 108(8): 2755 - 2763.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
T. D. Shanafelt, T. E. Witzig, S. R. Fink, R. B. Jenkins, S. F. Paternoster, S. A. Smoley, K. J. Stockero, D. M. Nast, H. C. Flynn, R. C. Tschumper, et al.
Prospective Evaluation of Clonal Evolution During Long-Term Follow-Up of Patients With Untreated Early-Stage Chronic Lymphocytic Leukemia
J. Clin. Oncol., October 1, 2006; 24(28): 4634 - 4641.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
M. Dong and G. C. Blobe
Role of transforming growth factor-beta in hematologic malignancies
Blood, June 15, 2006; 107(12): 4589 - 4596.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
T. Haferlach, A. Kohlmann, S. Schnittger, M. Dugas, W. Hiddemann, W. Kern, and C. Schoch
Global approach to the diagnosis of leukemia using gene expression profiling
Blood, August 15, 2005; 106(4): 1189 - 1198.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
E. Mikaelsson, A. H. Danesh-Manesh, A. Luppert, M. Jeddi-Tehrani, M.-R. Rezvany, R. A. Sharifian, R. Safaie, A. Roohi, A. Osterborg, F. Shokri, et al.
Fibromodulin, an extracellular matrix protein: characterization of its unique gene and protein expression in B-cell chronic lymphocytic leukemia and mantle cell lymphoma
Blood, June 15, 2005; 105(12): 4828 - 4835.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
C. Mayr, D. Bund, M. Schlee, A. Moosmann, D. M. Kofler, M. Hallek, and C.-M. Wendtner
Fibromodulin as a novel tumor-associated antigen (TAA) in chronic lymphocytic leukemia (CLL), which allows expansion of specific CD8+ autologous T lymphocytes
Blood, February 15, 2005; 105(4): 1566 - 1573.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
T. D. Shanafelt, S. M. Geyer, and N. E. Kay
Prognosis at diagnosis: integrating molecular biologic insights into clinical practice for patients with CLL
Blood, February 15, 2004; 103(4): 1202 - 1210.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2003 by the American Association for Cancer Research.