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 language | English |
|---|---|
| Pages (from-to) | 90-100 |
| Number of pages | 11 |
| Journal | Immunologic Research |
| Volume | 63 |
| Issue number | 1-3 |
| DOIs | |
| Publication status | Published - Dec 1 2015 |
Fingerprint
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 journal › Article
}
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
UR - http://www.scopus.com/inward/record.url?scp=84947491446&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84947491446&partnerID=8YFLogxK
U2 - 10.1007/s12026-015-8688-3
DO - 10.1007/s12026-015-8688-3
M3 - Article
VL - 63
SP - 90
EP - 100
JO - Immunologic Research
JF - Immunologic Research
SN - 0257-277X
IS - 1-3
ER -