TY - JOUR
T1 - A seven-gene expression panel distinguishing clonal expansions of pre-leukemic and chronic lymphocytic leukemia B cells from normal B lymphocytes
AU - McCarthy, Brian A.
AU - Yancopoulos, Sophia
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
PY - 2015/12/1
Y1 - 2015/12/1
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.
KW - B lymphocytes
KW - Chronic lymphocytic leukemia
KW - Diagnosis
KW - Gene expression
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U2 - 10.1007/s12026-015-8688-3
DO - 10.1007/s12026-015-8688-3
M3 - Article
C2 - 26318878
AN - SCOPUS:84947491446
VL - 63
SP - 90
EP - 100
JO - Immunologic Research
JF - Immunologic Research
SN - 0257-277X
IS - 1-3
ER -