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

Brian A. McCarthy, Sophia Yancopoulos, Mike Tipping, Xiao jie Yan, Xue Ping Wang, Fiona Bennett, Wentian Li, Martin Lesser, Santanu Paul, Erin Boyle, Carolina Moreno, Rosa Catera, Bradley T. Messmer, Giovanna Cutrona, Manlio Ferrarini, Jonathan E. Kolitz, Steven L. Allen, Kanti R. Rai, Andrew C. Rawstron, Nicholas Chiorazzi

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)90-100
Number of pages11
JournalImmunologic Research
Volume63
Issue number1-3
DOIs
Publication statusPublished - Dec 1 2015

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B-Cell Chronic Lymphocytic Leukemia
Lymphocytosis
B-Lymphocytes
Gene Expression
Genes
Microarray Analysis
ROC Curve
Population
Learning

Keywords

  • B lymphocytes
  • Chronic lymphocytic leukemia
  • Diagnosis
  • Gene expression

ASJC Scopus subject areas

  • Immunology

Cite this

A seven-gene expression panel distinguishing clonal expansions of pre-leukemic and chronic lymphocytic leukemia B cells from normal B lymphocytes. / McCarthy, Brian A.; Yancopoulos, Sophia; Tipping, Mike; Yan, Xiao jie; Wang, Xue Ping; Bennett, Fiona; Li, Wentian; Lesser, Martin; Paul, Santanu; Boyle, Erin; Moreno, Carolina; Catera, Rosa; Messmer, Bradley T.; Cutrona, Giovanna; Ferrarini, Manlio; Kolitz, Jonathan E.; Allen, Steven L.; Rai, Kanti R.; Rawstron, Andrew C.; Chiorazzi, Nicholas.

In: Immunologic Research, Vol. 63, No. 1-3, 01.12.2015, p. 90-100.

Research output: Contribution to journalArticle

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 & Chiorazzi, N 2015, 'A seven-gene expression panel distinguishing clonal expansions of pre-leukemic and chronic lymphocytic leukemia B cells from normal B lymphocytes', Immunologic Research, vol. 63, no. 1-3, pp. 90-100. https://doi.org/10.1007/s12026-015-8688-3
McCarthy, Brian A. ; Yancopoulos, Sophia ; Tipping, Mike ; Yan, Xiao jie ; Wang, Xue Ping ; Bennett, Fiona ; Li, Wentian ; Lesser, Martin ; Paul, Santanu ; Boyle, Erin ; Moreno, Carolina ; Catera, Rosa ; Messmer, Bradley T. ; Cutrona, Giovanna ; Ferrarini, Manlio ; Kolitz, Jonathan E. ; Allen, Steven L. ; Rai, Kanti R. ; Rawstron, Andrew C. ; Chiorazzi, Nicholas. / A seven-gene expression panel distinguishing clonal expansions of pre-leukemic and chronic lymphocytic leukemia B cells from normal B lymphocytes. In: Immunologic Research. 2015 ; Vol. 63, No. 1-3. pp. 90-100.
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AU - Tipping, Mike

AU - Yan, Xiao jie

AU - Wang, Xue Ping

AU - Bennett, Fiona

AU - Li, Wentian

AU - Lesser, Martin

AU - Paul, Santanu

AU - Boyle, Erin

AU - Moreno, Carolina

AU - Catera, Rosa

AU - Messmer, Bradley T.

AU - Cutrona, Giovanna

AU - Ferrarini, Manlio

AU - Kolitz, Jonathan E.

AU - Allen, Steven L.

AU - Rai, Kanti R.

AU - Rawstron, Andrew C.

AU - Chiorazzi, Nicholas

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N2 - 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.

AB - 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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KW - Diagnosis

KW - Gene expression

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