A seven-gene expression panel distinguishing clonal expansions of pre-leukemic and chronic lymphocytic leukemia B cells
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CANCER IMMUNOLOGY
A seven-gene expression panel distinguishing clonal expansions of pre-leukemic and chronic lymphocytic leukemia B cells from normal B lymphocytes Brian A. McCarthy1 • Sophia Yancopoulos1 • Mike Tipping2 • Xiao-jie Yan1 Xue Ping Wang1 • Fiona Bennett3 • Wentian Li1 • Martin Lesser1 • Santanu Paul1 • Erin Boyle1 • Carolina Moreno1 • Rosa Catera1 • Bradley T. Messmer4 • Giovanna Cutrona5 • Manlio Ferrarini6 • Jonathan E. Kolitz1,7 • Steven L. Allen1,7 • Kanti R. Rai1,7 • Andrew C. Rawstron3 • Nicholas Chiorazzi1,7
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Nicholas Chiorazzi
Ó Springer Science+Business Media New York 2015
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. Keywords
Chronic lymphocytic leukemia Diagnosis Gene expression B lymphocytes
Electronic supplementary material The online version of this article (doi:10.1007/s12026-015-8688-3) contains supplementary material, which is available to authorized users. & Nicholas Chiorazzi [email protected]
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U.O. Molecular Pathology, IRCCS Azienda Ospedaliera Universitaria San Martino – Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
The Feinstein Institute for Medical Research, Manhasset, NY 11030, USA
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IRCCS Azienda Ospedaliera Universitaria San Martino – Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
Vector Anomaly, Suffolk IP23 8HB, UK
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Haematological Malignancy Diagnostic Service, Leeds Teaching Hospitals, Leeds LS2 9JT, UK
Departments of Molecular Medicine and Medicine, Hofstra North Shore-LIJ School of Medicine, Hempstead, NY 11549-1000, USA
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Moores Cancer Center, University of California, San Diego, San Diego, CA 92093, US
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