Identification of a global gene expression signature of B-chronic lymphocytic leukemia.
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.
Jelinek
Diane F
DF
Department of Immunology, Mayo Graduate and Medical Schools, Mayo Clinic, Rochester, MN 55905, USA. jelinek.diane@mayo.edu
Tschumper
Renee C
RC
Stolovitzky
Gustavo A
GA
Iturria
Stephen J
SJ
Tu
Yuhai
Y
Lepre
Jorge
J
Shah
Nigam
N
Kay
Neil E
NE
D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000328:Adult; D000465:Algorithms; D002352:Carrier Proteins / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D016326:Extracellular Matrix Proteins; D000071235:Fibromodulin; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D051821:Lymphoid Enhancer-Binding Factor 1; D008957:Models, Genetic; D015999:Multivariate Analysis; D011509:Proteoglycans / Q000235:genetics; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012984:Software; D014157:Transcription Factors / Q000235:genetics; D020666:ras-GRF1 / Q000235:genetics
C434046:ABCA6 protein, human; D018528:ATP-Binding Cassette Transporters; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D016326:Extracellular Matrix Proteins; C000604330:FMOD protein, human; D018974:Insulin-Like Growth Factor Binding Protein 4; D051821:Lymphoid Enhancer-Binding Factor 1; D011509:Proteoglycans; D018125:Receptors, Transforming Growth Factor beta; D014157:Transcription Factors; D020666:ras-GRF1; D000071235:Fibromodulin; C071736:betaglycan