title: Relation of gene expression phenotype to immunoglobulin mutation genotype in B cell chronic lymphocytic leukemia.
abstract: 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.
authors.affiliation: Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: A
authors.initials: A
authors.lastname: Rosenwald
authors.forename: A A
authors.initials: AA
authors.lastname: Alizadeh
authors.forename: G
authors.initials: G
authors.lastname: Widhopf
authors.forename: R
authors.initials: R
authors.lastname: Simon
authors.forename: R E
authors.initials: RE
authors.lastname: Davis
authors.forename: X
authors.initials: X
authors.lastname: Yu
authors.forename: L
authors.initials: L
authors.lastname: Yang
authors.forename: O K
authors.initials: OK
authors.lastname: Pickeral
authors.forename: L Z
authors.initials: LZ
authors.lastname: Rassenti
authors.forename: J
authors.initials: J
authors.lastname: Powell
authors.forename: D
authors.initials: D
authors.lastname: Botstein
authors.forename: J C
authors.initials: JC
authors.lastname: Byrd
authors.forename: M R
authors.initials: MR
authors.lastname: Grever
authors.forename: B D
authors.initials: BD
authors.lastname: Cheson
authors.forename: N
authors.initials: N
authors.lastname: Chiorazzi
authors.forename: W H
authors.initials: WH
authors.lastname: Wilson
authors.forename: T J
authors.initials: TJ
authors.lastname: Kipps
authors.forename: P O
authors.initials: PO
authors.lastname: Brown
authors.forename: L M
authors.initials: LM
authors.lastname: Staudt
mesh_terms: D015870:Gene Expression; D005838:Genotype; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics*; D016130:Immunophenotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D009154:Mutation
chemical_list: D007136:Immunoglobulins