ATM, CTLA4, MNDA, and HEM1 in high versus low CD38-expressing B-cell chronic lymphocytic leukemia

Avadhut D. Joshi, Ganapati V. Hegde, John D. Dickinson, Amit K. Mittal, James C. Lynch, James D. Eudy, James O. Armitage, Philip J. Bierman, R. Gregory Bociek, Marcel P. Devetten, Julie M. Vose, Shantaram S. Joshi

Research output: Contribution to journalArticle

Abstract

Purpose: In B-cell chronic lymphocytic leukemia (CLL), high CD38 expression has been associated with unfavorable clinical course, advanced disease, resistance to therapy, shorter time to first treatment, and shorter survival. However, the genes associated with CLL patient subgroups with high and low CD38 expression and their potential role in disease progression is not known. Experimental Design: To identify the genes associated with the clinical disparity in CLL patients with high versus low CD38 expression, transcriptional profiles were obtained from CLL cells from 39 different patients using oligonucleotide microarray. Gene expression was also compared between CLL cells and B cells from healthy individuals. Results: Gene expression analysis identified 76 differentially expressed genes in CD38 high versus low groups. Out of these genes, HEM1, CTLA4, and MNDA were selected for further studies and their differential expression was confirmed by real-time PCR. HEM1 overexpression was associated with poor outcome, whereas the overexpression of CTLA4 and MNDA was associated with good outcome. Down-regulation of HEM1 expression in patient CLL cells resulted in a significant increase in their susceptibility to fludarabine-mediated killing. In addition, when gene expression patterns in CD38 high and low CLL cells were compared with normal B-cell profiles, ATM expression was found to be significantly lower in CD38 high compared with CD38 low CLL as confirmed by real-time reverse transcription-PCR. Conclusions: These results identify the possible genes that may be involved in cell proliferation and survival and, thus, determining the clinical behavior of CLL patients expressing high or low CD38.

Original languageEnglish (US)
Pages (from-to)5295-5304
Number of pages10
JournalClinical Cancer Research
Volume13
Issue number18
DOIs
StatePublished - Sep 15 2007
Externally publishedYes

Fingerprint

B-Cell Chronic Lymphocytic Leukemia
Genes
Gene Expression
B-Lymphocytes
Disease Resistance
Oligonucleotide Array Sequence Analysis
Reverse Transcription
Disease Progression
Real-Time Polymerase Chain Reaction
Cell Survival
Research Design
Down-Regulation
Cell Proliferation
Polymerase Chain Reaction
Survival
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Joshi, A. D., Hegde, G. V., Dickinson, J. D., Mittal, A. K., Lynch, J. C., Eudy, J. D., ... Joshi, S. S. (2007). ATM, CTLA4, MNDA, and HEM1 in high versus low CD38-expressing B-cell chronic lymphocytic leukemia. Clinical Cancer Research, 13(18), 5295-5304. https://doi.org/10.1158/1078-0432.CCR-07-0283

ATM, CTLA4, MNDA, and HEM1 in high versus low CD38-expressing B-cell chronic lymphocytic leukemia. / Joshi, Avadhut D.; Hegde, Ganapati V.; Dickinson, John D.; Mittal, Amit K.; Lynch, James C.; Eudy, James D.; Armitage, James O.; Bierman, Philip J.; Bociek, R. Gregory; Devetten, Marcel P.; Vose, Julie M.; Joshi, Shantaram S.

In: Clinical Cancer Research, Vol. 13, No. 18, 15.09.2007, p. 5295-5304.

Research output: Contribution to journalArticle

Joshi, AD, Hegde, GV, Dickinson, JD, Mittal, AK, Lynch, JC, Eudy, JD, Armitage, JO, Bierman, PJ, Bociek, RG, Devetten, MP, Vose, JM & Joshi, SS 2007, 'ATM, CTLA4, MNDA, and HEM1 in high versus low CD38-expressing B-cell chronic lymphocytic leukemia', Clinical Cancer Research, vol. 13, no. 18, pp. 5295-5304. https://doi.org/10.1158/1078-0432.CCR-07-0283
Joshi, Avadhut D. ; Hegde, Ganapati V. ; Dickinson, John D. ; Mittal, Amit K. ; Lynch, James C. ; Eudy, James D. ; Armitage, James O. ; Bierman, Philip J. ; Bociek, R. Gregory ; Devetten, Marcel P. ; Vose, Julie M. ; Joshi, Shantaram S. / ATM, CTLA4, MNDA, and HEM1 in high versus low CD38-expressing B-cell chronic lymphocytic leukemia. In: Clinical Cancer Research. 2007 ; Vol. 13, No. 18. pp. 5295-5304.
@article{2647f4e08e2f4998b1984d23457c7fda,
title = "ATM, CTLA4, MNDA, and HEM1 in high versus low CD38-expressing B-cell chronic lymphocytic leukemia",
abstract = "Purpose: In B-cell chronic lymphocytic leukemia (CLL), high CD38 expression has been associated with unfavorable clinical course, advanced disease, resistance to therapy, shorter time to first treatment, and shorter survival. However, the genes associated with CLL patient subgroups with high and low CD38 expression and their potential role in disease progression is not known. Experimental Design: To identify the genes associated with the clinical disparity in CLL patients with high versus low CD38 expression, transcriptional profiles were obtained from CLL cells from 39 different patients using oligonucleotide microarray. Gene expression was also compared between CLL cells and B cells from healthy individuals. Results: Gene expression analysis identified 76 differentially expressed genes in CD38 high versus low groups. Out of these genes, HEM1, CTLA4, and MNDA were selected for further studies and their differential expression was confirmed by real-time PCR. HEM1 overexpression was associated with poor outcome, whereas the overexpression of CTLA4 and MNDA was associated with good outcome. Down-regulation of HEM1 expression in patient CLL cells resulted in a significant increase in their susceptibility to fludarabine-mediated killing. In addition, when gene expression patterns in CD38 high and low CLL cells were compared with normal B-cell profiles, ATM expression was found to be significantly lower in CD38 high compared with CD38 low CLL as confirmed by real-time reverse transcription-PCR. Conclusions: These results identify the possible genes that may be involved in cell proliferation and survival and, thus, determining the clinical behavior of CLL patients expressing high or low CD38.",
author = "Joshi, {Avadhut D.} and Hegde, {Ganapati V.} and Dickinson, {John D.} and Mittal, {Amit K.} and Lynch, {James C.} and Eudy, {James D.} and Armitage, {James O.} and Bierman, {Philip J.} and Bociek, {R. Gregory} and Devetten, {Marcel P.} and Vose, {Julie M.} and Joshi, {Shantaram S.}",
year = "2007",
month = "9",
day = "15",
doi = "10.1158/1078-0432.CCR-07-0283",
language = "English (US)",
volume = "13",
pages = "5295--5304",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "18",

}

TY - JOUR

T1 - ATM, CTLA4, MNDA, and HEM1 in high versus low CD38-expressing B-cell chronic lymphocytic leukemia

AU - Joshi, Avadhut D.

AU - Hegde, Ganapati V.

AU - Dickinson, John D.

AU - Mittal, Amit K.

AU - Lynch, James C.

AU - Eudy, James D.

AU - Armitage, James O.

AU - Bierman, Philip J.

AU - Bociek, R. Gregory

AU - Devetten, Marcel P.

AU - Vose, Julie M.

AU - Joshi, Shantaram S.

PY - 2007/9/15

Y1 - 2007/9/15

N2 - Purpose: In B-cell chronic lymphocytic leukemia (CLL), high CD38 expression has been associated with unfavorable clinical course, advanced disease, resistance to therapy, shorter time to first treatment, and shorter survival. However, the genes associated with CLL patient subgroups with high and low CD38 expression and their potential role in disease progression is not known. Experimental Design: To identify the genes associated with the clinical disparity in CLL patients with high versus low CD38 expression, transcriptional profiles were obtained from CLL cells from 39 different patients using oligonucleotide microarray. Gene expression was also compared between CLL cells and B cells from healthy individuals. Results: Gene expression analysis identified 76 differentially expressed genes in CD38 high versus low groups. Out of these genes, HEM1, CTLA4, and MNDA were selected for further studies and their differential expression was confirmed by real-time PCR. HEM1 overexpression was associated with poor outcome, whereas the overexpression of CTLA4 and MNDA was associated with good outcome. Down-regulation of HEM1 expression in patient CLL cells resulted in a significant increase in their susceptibility to fludarabine-mediated killing. In addition, when gene expression patterns in CD38 high and low CLL cells were compared with normal B-cell profiles, ATM expression was found to be significantly lower in CD38 high compared with CD38 low CLL as confirmed by real-time reverse transcription-PCR. Conclusions: These results identify the possible genes that may be involved in cell proliferation and survival and, thus, determining the clinical behavior of CLL patients expressing high or low CD38.

AB - Purpose: In B-cell chronic lymphocytic leukemia (CLL), high CD38 expression has been associated with unfavorable clinical course, advanced disease, resistance to therapy, shorter time to first treatment, and shorter survival. However, the genes associated with CLL patient subgroups with high and low CD38 expression and their potential role in disease progression is not known. Experimental Design: To identify the genes associated with the clinical disparity in CLL patients with high versus low CD38 expression, transcriptional profiles were obtained from CLL cells from 39 different patients using oligonucleotide microarray. Gene expression was also compared between CLL cells and B cells from healthy individuals. Results: Gene expression analysis identified 76 differentially expressed genes in CD38 high versus low groups. Out of these genes, HEM1, CTLA4, and MNDA were selected for further studies and their differential expression was confirmed by real-time PCR. HEM1 overexpression was associated with poor outcome, whereas the overexpression of CTLA4 and MNDA was associated with good outcome. Down-regulation of HEM1 expression in patient CLL cells resulted in a significant increase in their susceptibility to fludarabine-mediated killing. In addition, when gene expression patterns in CD38 high and low CLL cells were compared with normal B-cell profiles, ATM expression was found to be significantly lower in CD38 high compared with CD38 low CLL as confirmed by real-time reverse transcription-PCR. Conclusions: These results identify the possible genes that may be involved in cell proliferation and survival and, thus, determining the clinical behavior of CLL patients expressing high or low CD38.

UR - http://www.scopus.com/inward/record.url?scp=34848829606&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34848829606&partnerID=8YFLogxK

U2 - 10.1158/1078-0432.CCR-07-0283

DO - 10.1158/1078-0432.CCR-07-0283

M3 - Article

C2 - 17875758

AN - SCOPUS:34848829606

VL - 13

SP - 5295

EP - 5304

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 18

ER -