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

Authors

B. A. McCarthy, Northwell Health
S. Yancopoulos, Northwell Health
X. J. Yan, Northwell Health
X. P. Wang, Northwell Health
W. Li, Northwell Health
M. Lesser, Hofstra Northwell School of Medicine
S. Paul, Northwell Health
E. Boyle, Northwell Health
C. Moreno, Northwell Health
R. Catera, Northwell Health
B. T. Messmer, Northwell Health
J. E. Kolitz, Hofstra Northwell School of Medicine
S. L. Allen, Hofstra Northwell School of Medicine
K. R. Rai, Hofstra Northwell School of Medicine
N. Chiorazzi, Hofstra Northwell School of Medicine
+5 additional authors

Publication Date

2015

Journal Title

Immunol Res

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.

Volume Number

63

Issue Number

1-3

Pages

90-100

Document Type

Article

EPub Date

2015/09/01

Status

Faculty, Northwell Researcher

Facility

School of Medicine; Northwell Health

Primary Department

Molecular Medicine

Additional Departments

Hematology/Medical Oncology; General Internal Medicine; Occupational Medicine, Epidemiology and Prevention

PMID

26318878

DOI

10.1007/s12026-015-8688-3