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

Autor: McCarthy BA; The Feinstein Institute for Medical Research, Manhasset, NY, 11030, USA., Yancopoulos S; The Feinstein Institute for Medical Research, Manhasset, NY, 11030, USA., Tipping M; Vector Anomaly, Suffolk, IP23 8HB, UK., Yan XJ; The Feinstein Institute for Medical Research, Manhasset, NY, 11030, USA., Wang XP; The Feinstein Institute for Medical Research, Manhasset, NY, 11030, USA., Bennett F; Haematological Malignancy Diagnostic Service, Leeds Teaching Hospitals, Leeds, LS2 9JT, UK., Li W; The Feinstein Institute for Medical Research, Manhasset, NY, 11030, USA., Lesser M; The Feinstein Institute for Medical Research, Manhasset, NY, 11030, USA., Paul S; The Feinstein Institute for Medical Research, Manhasset, NY, 11030, USA., Boyle E; The Feinstein Institute for Medical Research, Manhasset, NY, 11030, USA., Moreno C; The Feinstein Institute for Medical Research, Manhasset, NY, 11030, USA., Catera R; The Feinstein Institute for Medical Research, Manhasset, NY, 11030, USA., Messmer BT; Moores Cancer Center, University of California, San Diego, San Diego, CA, 92093, USA., Cutrona G; U.O. Molecular Pathology, IRCCS Azienda Ospedaliera Universitaria San Martino - Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy., Ferrarini M; IRCCS Azienda Ospedaliera Universitaria San Martino - Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy., Kolitz JE; The Feinstein Institute for Medical Research, Manhasset, NY, 11030, USA.; Departments of Molecular Medicine and Medicine, Hofstra North Shore-LIJ School of Medicine, Hempstead, NY, 11549-1000, USA., Allen SL; The Feinstein Institute for Medical Research, Manhasset, NY, 11030, USA.; Departments of Molecular Medicine and Medicine, Hofstra North Shore-LIJ School of Medicine, Hempstead, NY, 11549-1000, USA., Rai KR; The Feinstein Institute for Medical Research, Manhasset, NY, 11030, USA.; Departments of Molecular Medicine and Medicine, Hofstra North Shore-LIJ School of Medicine, Hempstead, NY, 11549-1000, USA., Rawstron AC; Haematological Malignancy Diagnostic Service, Leeds Teaching Hospitals, Leeds, LS2 9JT, UK., Chiorazzi N; The Feinstein Institute for Medical Research, Manhasset, NY, 11030, USA. nchizzi@NSHS.edu.; Departments of Molecular Medicine and Medicine, Hofstra North Shore-LIJ School of Medicine, Hempstead, NY, 11549-1000, USA. nchizzi@NSHS.edu.
Jazyk: angličtina
Zdroj: Immunologic research [Immunol Res] 2015 Dec; Vol. 63 (1-3), pp. 90-100.
DOI: 10.1007/s12026-015-8688-3
Abstrakt: 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.
Databáze: MEDLINE
Externí odkaz: