title: A seven-gene expression panel distinguishing clonal expansions of pre-leukemic and chronic lymphocytic leukemia B cells from normal B lymphocytes.
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.
authors: The Feinstein Institute for Medical Research, Manhasset, NY, 11030, USA.
authors: Brian A
authors: BA
authors: McCarthy
authors: The Feinstein Institute for Medical Research, Manhasset, NY, 11030, USA.
authors: Sophia
authors: S
authors: Yancopoulos
authors: Vector Anomaly, Suffolk, IP23 8HB, UK.
authors: Mike
authors: M
authors: Tipping
authors: The Feinstein Institute for Medical Research, Manhasset, NY, 11030, USA.
authors: Xiao-Jie
authors: XJ
authors: Yan
authors: The Feinstein Institute for Medical Research, Manhasset, NY, 11030, USA.
authors: Xue Ping
authors: XP
authors: Wang
authors: Haematological Malignancy Diagnostic Service, Leeds Teaching Hospitals, Leeds, LS2 9JT, UK.
authors: Fiona
authors: F
authors: Bennett
authors: The Feinstein Institute for Medical Research, Manhasset, NY, 11030, USA.
authors: Wentian
authors: W
authors: Li
authors: The Feinstein Institute for Medical Research, Manhasset, NY, 11030, USA.
authors: Martin
authors: M
authors: Lesser
authors: The Feinstein Institute for Medical Research, Manhasset, NY, 11030, USA.
authors: Santanu
authors: S
authors: Paul
authors: The Feinstein Institute for Medical Research, Manhasset, NY, 11030, USA.
authors: Erin
authors: E
authors: Boyle
authors: The Feinstein Institute for Medical Research, Manhasset, NY, 11030, USA.
authors: Carolina
authors: C
authors: Moreno
authors: The Feinstein Institute for Medical Research, Manhasset, NY, 11030, USA.
authors: Rosa
authors: R
authors: Catera
authors: Moores Cancer Center, University of California, San Diego, San Diego, CA, 92093, USA.
authors: Bradley T
authors: BT
authors: Messmer
authors: U.O. Molecular Pathology, IRCCS Azienda Ospedaliera Universitaria San Martino - Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
authors: Giovanna
authors: G
authors: Cutrona
authors: IRCCS Azienda Ospedaliera Universitaria San Martino - Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
authors: Manlio
authors: M
authors: Ferrarini
authors: 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.
authors: Jonathan E
authors: JE
authors: Kolitz
authors: 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.
authors: Steven L
authors: SL
authors: Allen
authors: 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.
authors: Kanti R
authors: KR
authors: Rai
authors: Haematological Malignancy Diagnostic Service, Leeds Teaching Hospitals, Leeds, LS2 9JT, UK.
authors: Andrew C
authors: AC
authors: Rawstron
authors: 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.
authors: Nicholas
authors: N
authors: Chiorazzi
mesh_terms: D001402:B-Lymphocytes / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D058541:Class II Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D019295:Computational Biology; D003937:Diagnosis, Differential; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D000071235:Fibromodulin; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis* / Q000235:genetics; D008213:Lymphocyte Activation / Q000235:genetics; D008218:Lymphocytosis / Q000175:diagnosis* / Q000235:genetics; D046228:Microarray Analysis; D011230:Precancerous Conditions / Q000175:diagnosis* / Q000235:genetics; D011237:Predictive Value of Tests; D011379:Prognosis; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism*; D059467:Transcriptome
chemical_list: D016326:Extracellular Matrix Proteins; C000604330:FMOD protein, human; D011509:Proteoglycans; D000071235:Fibromodulin; D058541:Class II Phosphatidylinositol 3-Kinases; C502616:PIK3C2B protein, human
keywords: B lymphocytes; Chronic lymphocytic leukemia; Diagnosis; Gene expression