The Journal of Experimental Medicine
Translational Medicine Lupus Symposium
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Published 3 December 2001. doi:10.1084/jem.194.11.1639
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© Rockefeller University Press, 0022-1007/2001/12/1639/ $5.00
The Journal of Experimental Medicine, Volume 194, Number 11, December 3, 2001 1639-1648

Original Article

 Relation of Gene Expression Phenotype to Immunoglobulin Mutation Genotype in B Cell Chronic Lymphocytic Leukemia

Andreas Rosenwald1, Ash A. Alizadeh2, George Widhopf5, Richard Simon6, R. Eric Davis1, Xin Yu1, Liming Yang1, Oxana K. Pickeral1, Laura Z. Rassenti5, John Powell7, David Botstein3, John C. Byrd8, Michael R. Grever9, Bruce D. Cheson10, Nicholas Chiorazzi11, Wyndham H. Wilson12, Thomas J. Kipps5, Patrick O. Brown2,4 and Louis M. Staudt1

1 Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
2 Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305
3 Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305
4 The Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305
5 University of California at San Diego, Department of Medicine, La Jolla, CA 92093
6 Biometric Research Branch, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
7 Bioinformatics and Molecular Analysis Section, CBEL, CIT, National Institutes of Health, Bethesda, MD 20892
8 Department of Medicine, Walter Reed Army Medical Center, Washington, D.C. 20307
9 Department of Internal Medicine, Ohio State University, Columbus, OH 43214
10 CTEP, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
11 North Shore-Long Island Jewish Research Institute, Manhasset, NY 11030
12 Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892

Address correspondence to Louis M. Staudt, Metabolism Branch, National Cancer Institute, Bldg. 10, Rm. 4N114, Bethesda, MD 20892. Phone: 301-402-1892; Fax: 301-496-9956; E-mail: lstaudt{at}box-l.nih.gov

The most common human leukemia is B cell chronic lymphocytic leukemia (CLL), a malignancy of mature B cells with a characteristic clinical presentation but a variable clinical course. The rearranged immunoglobulin (Ig) genes of CLL cells may be either germ-line in sequence or somatically mutated. Lack of Ig mutations defined a distinctly worse prognostic group of CLL patients raising the possibility that CLL comprises two distinct diseases. Using genomic-scale gene expression profiling, we show that CLL is characterized by a common gene expression "signature," irrespective of Ig mutational status, suggesting that CLL cases share a common mechanism of transformation and/or cell of origin. Nonetheless, the expression of hundreds of other genes correlated with the Ig mutational status, including many genes that are modulated in expression during mitogenic B cell receptor signaling. These genes were used to build a CLL subtype predictor that may help in the clinical classification of patients with this disease.

Key Words: cDNA microarrays • gene expression profiling • leukemia • lymphocytic • chronic


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