Document Detail


Enhanced detection of chromosomal abnormalities in chronic lymphocytic leukemia by conventional cytogenetics using CpG oligonucleotide in combination with pokeweed mitogen and phorbol myristate acetate.
MedLine Citation:
PMID:  21494579     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Reproducible cytogenetic analysis in CLL has been limited by the inability to obtain reliable metaphase cells for analysis. CpG oligonucleotide and cytokine stimulation have been shown to improve metaphase analysis of CLL cytogenetic abnormalities, but is limited by variability in the cytokine receptor levels, stability and biological activity of the cytokine in culture conditions and high costs associated with these reagents. We report here use of a novel, stable CpG, GNKG168 along with pokeweed mitogen (PWM) and phorbol 12-myristate 13-acetate (PMA) for conventional cytogenetic assessment in CLL. We demonstrate that the combined use of GNKG168+PWM/PMA increased the sensitivity of detection of chromosomal abnormalities compared to PWM/PMA (n=207, odds ratio=2.2, p=0.0002) and GNKG168 (n=219, odds ratio=1.5, p=0.0452). Further, a significant increase in sensitivity to detect complexity ≥3 with GNKG168+PWM/PMA compared to GNKG168 alone (odds ratio 8.0, p=0.0022) or PWM/PMA alone (odds ratio 9.6, p=0.0007) was observed. The trend toward detection of higher complexity was significantly greater with GNKG168+PWM/PMA compared to GNKG168 alone (p=0.0412). The increased sensitivity was mainly attributed to the addition of PWM/PMA with GNKG168 because GNKG168 alone showed no difference in sensitivity for detection of complex abnormalities (p=0.17). Comparison of fluorescence in situ hybridization (FISH) results with karyotypic results showed a high degree of consistency, although some complex karyotypes were present in cases with no adverse FISH abnormality. These studies provide evidence for potential use of GNKG168 in combination with PWM and PMA in karyotypic analysis of CLL patient samples to better identify chromosomal abnormalities for risk stratification.
Authors:
Natarajan Muthusamy; Heather Breidenbach; Leslie Andritsos; Joseph Flynn; Jeffrey Jones; Asha Ramanunni; Xiaokui Mo; David Jarjoura; John C Byrd; Nyla A Heerema
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cancer genetics     Volume:  204     ISSN:  2210-7762     ISO Abbreviation:  Cancer Genet     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-04-20     Completed Date:  2011-06-13     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  101539150     Medline TA:  Cancer Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  77-83     Citation Subset:  IM    
Affiliation:
Division of Hematology, The OSU Comprehensive Cancer Center, The Ohio State University, Columbus, USA. raj.muthusamy@osumc.edu
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
Chromosome Aberrations*
Humans
Karyotyping / methods*
Leukemia, Lymphocytic, Chronic, B-Cell / diagnosis*,  genetics*
Middle Aged
Oligodeoxyribonucleotides / diagnostic use
Pokeweed Mitogens / diagnostic use
Sensitivity and Specificity
Tetradecanoylphorbol Acetate / diagnostic use
Grant Support
ID/Acronym/Agency:
1K12 CA133250/CA/NCI NIH HHS; P01 CA101956/CA/NCI NIH HHS; P01 CA95426/CA/NCI NIH HHS; P50 CA140158/CA/NCI NIH HHS; P50 CA140158-03/CA/NCI NIH HHS; P50-CA140158/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/GNKG168; 0/Oligodeoxyribonucleotides; 0/Pokeweed Mitogens; 16561-29-8/Tetradecanoylphorbol Acetate
Comments/Corrections

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