1. A seven-gene expression panel distinguishing clonal expansions of pre-leukemic and chronic lymphocytic leukemia B cells from normal B lymphocytes.
- Author
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McCarthy BA, Yancopoulos S, Tipping M, Yan XJ, Wang XP, Bennett F, Li W, Lesser M, Paul S, Boyle E, Moreno C, Catera R, Messmer BT, Cutrona G, Ferrarini M, Kolitz JE, Allen SL, Rai KR, Rawstron AC, and Chiorazzi N
- Subjects
- Cell Line, Tumor, Cell Proliferation genetics, Class II Phosphatidylinositol 3-Kinases genetics, Computational Biology, Diagnosis, Differential, Extracellular Matrix Proteins genetics, Fibromodulin, Gene Expression Regulation, Neoplastic, Humans, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Lymphocyte Activation genetics, Lymphocytosis genetics, Microarray Analysis, Precancerous Conditions genetics, Prognosis, Proteoglycans genetics, Transcriptome, B-Lymphocytes physiology, Class II Phosphatidylinositol 3-Kinases metabolism, Extracellular Matrix Proteins metabolism, Leukemia, Lymphocytic, Chronic, B-Cell diagnosis, Lymphocytosis diagnosis, Precancerous Conditions diagnosis, Predictive Value of Tests, Proteoglycans metabolism
- Abstract
Chronic lymphocytic leukemia (CLL) is a clonal disease of B lymphocytes manifesting as an absolute lymphocytosis in the blood. However, not all lymphocytoses are leukemic. In addition, first-degree relatives of CLL patients have an ~15 % chance of developing a precursor condition to CLL termed monoclonal B cell lymphocytosis (MBL), and distinguishing CLL and MBL B lymphocytes from normal B cell expansions can be a challenge. Therefore, we selected FMOD, CKAP4, PIK3C2B, LEF1, PFTK1, BCL-2, and GPM6a from a set of genes significantly differentially expressed in microarray analyses that compared CLL cells with normal B lymphocytes and used these to determine whether we could discriminate CLL and MBL cells from B cells of healthy controls. Analysis with receiver operating characteristics and Bayesian relevance determination demonstrated good concordance with all panel genes. Using a random forest classifier, the seven-gene panel reliably distinguished normal polyclonal B cell populations from expression patterns occurring in pre-CLL and CLL B cell populations with an error rate of 2 %. Using Bayesian learning, the expression levels of only two genes, FMOD and PIK3C2B, correctly distinguished 100 % of CLL and MBL cases from normal polyclonal and mono/oligoclonal B lymphocytes. Thus, this study sets forth effective computational approaches that distinguish MBL/CLL from normal B lymphocytes. The findings also support the concept that MBL is a CLL precursor.
- Published
- 2015
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