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A seven-gene expression panel distinguishing clonal expansions of pre-leukemic and chronic lymphocytic leukemia B cells from normal B lymphocytes

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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.

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Acknowledgments

This work was supported in part by an RO-1 grant from the National Cancer Institute/NIH (CA081554) and by philanthropic contributions from The Karches Foundation, Marks Foundation, Jerome Levy Foundation, Leon Levy Foundation, and the Frank and Mildred Feinberg Foundation.

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Authors and Affiliations

  1. The Feinstein Institute for Medical Research, Manhasset, NY, 11030, USA

    Brian A. McCarthy, Sophia Yancopoulos, Xiao-jie Yan, Xue Ping Wang, Wentian Li, Martin Lesser, Santanu Paul, Erin Boyle, Carolina Moreno, Rosa Catera, Jonathan E. Kolitz, Steven L. Allen, Kanti R. Rai & Nicholas Chiorazzi

  2. Vector Anomaly, Suffolk, IP23 8HB, UK

    Mike Tipping

  3. Haematological Malignancy Diagnostic Service, Leeds Teaching Hospitals, Leeds, LS2 9JT, UK

    Fiona Bennett & Andrew C. Rawstron

  4. Moores Cancer Center, University of California, San Diego, San Diego, CA, 92093, USA

    Bradley T. Messmer

  5. U.O. Molecular Pathology, IRCCS Azienda Ospedaliera Universitaria San Martino – Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy

    Giovanna Cutrona

  6. IRCCS Azienda Ospedaliera Universitaria San Martino – Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy

    Manlio Ferrarini

  7. Departments of Molecular Medicine and Medicine, Hofstra North Shore-LIJ School of Medicine, Hempstead, NY, 11549-1000, USA

    Jonathan E. Kolitz, Steven L. Allen, Kanti R. Rai & Nicholas Chiorazzi

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  1. Brian A. McCarthy
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  2. Sophia Yancopoulos
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  3. Mike Tipping
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Correspondence to Nicholas Chiorazzi.

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McCarthy, B.A., Yancopoulos, S., Tipping, M. et al. A seven-gene expression panel distinguishing clonal expansions of pre-leukemic and chronic lymphocytic leukemia B cells from normal B lymphocytes. Immunol Res 63, 90–100 (2015). https://doi.org/10.1007/s12026-015-8688-3

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