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