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Bcl-2 level as a biomarker for 13q14 deletion in CLL
Article first published online: 2 AUG 2013
Copyright © 2013 International Clinical Cytometry Society
Cytometry Part B: Clinical Cytometry
Volume 84B, Issue 4, pages 237–247, July/August 2013
How to Cite
How to cite this article: Bcl-2 Level as a Biomarker for 13q14 Deletion in CLL. Cytometry Part B 2013; 84B: 237–247., , , , , , , , , .
This article is a US government work and, as such, is in the public domain in the United States of America.
- Issue published online: 2 AUG 2013
- Article first published online: 2 AUG 2013
- Manuscript Accepted: 6 MAR 2013
- Manuscript Revised: 4 MAR 2013
- Manuscript Received: 24 AUG 2012
- Oak Ridge Institute for Science and Education through US DOE and US FDA (Heba Degheidy's appointment to the Research Participation Program at CBER)
- Intramural Research Program of the National, Heart, Lung and Blood Institute, National Institutes of Health and the National Cancer Institute.
- chronic lymphocytic leukemia;
- flow cytometry;
- del 13q14;
- hemizygous/homozygous deletion
Deletion 13q14.3 is the most common cytogenetic abnormality in chronic lymphocytic leukemia (CLL). Previously it was reported that miR-15/16 is the target of 13q14 deletions and plays a tumor suppressor role by suppressing Bcl-2. Therefore, Bcl-2 expression was examined more closely to determine whether it would predict 13q14 deletion status.
A multi-color flow panel consisting of anti-Bcl-2/anti-lambda/anti-kappa/CD19/CD5/CD3/CD20 was performed. The ability of Bcl-2 to predict 13q14 deletion was tested using the conventional Bcl-2 index (c-index): mean fluorescence intensity (MFI) of CLL clone/MFI of residual T cells. Fifty-four untreated CLL/MBL patients were studied. Bimodal Bcl-2 expression was evaluated to test the ability of Bcl-2 to detect intraclonal heterogeneity. Other CLL prognostic markers including CD38, CD49d, CD26, and CD69 were evaluated. FISH was performed on selected sorted populations.
The Bcl-2 c-index strongly predicts del13q14 P < 0.0001. A statistically significant association was observed between the percentage of cells carrying the deletion and the level of Bcl-2 expression P < 0.05. Cells sorted based on Bcl-2 expression showed enrichment of both hemizygous and homozygous del 13q14 cells. Also, we observed that an alteration in Bcl-2 level over time predicts changes in 13q14 deletion status. And a statistically significant correlation between the bimodal pattern of CD69 expression and the presence of 13q14 deletion was found P < 0.0001.
Bcl-2 expression using the c-index strongly predicts 13q14 deletion and can be used to distinguish homozygous, heterozygous, and diploid CLL clonal cells. Further systematic studies of this biomarker are needed for confirmation and expansion of these findings. Published 2013 Wiley-Periodicals, Inc.