PMID- 21494579 OWN - NLM STAT- MEDLINE DCOM- 20110613 LR - 20220408 IS - 2210-7762 (Print) VI - 204 IP - 2 DP - 2011 Feb TI - Enhanced detection of chromosomal abnormalities in chronic lymphocytic leukemia by conventional cytogenetics using CpG oligonucleotide in combination with pokeweed mitogen and phorbol myristate acetate. PG - 77-83 LID - 10.1016/j.cancergen.2010.12.006 [doi] AB - 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. FAU - Muthusamy, Natarajan AU - Muthusamy N AD - Division of Hematology, The OSU Comprehensive Cancer Center, The Ohio State University, Columbus, USA. raj.muthusamy@osumc.edu FAU - Breidenbach, Heather AU - Breidenbach H FAU - Andritsos, Leslie AU - Andritsos L FAU - Flynn, Joseph AU - Flynn J FAU - Jones, Jeffrey AU - Jones J FAU - Ramanunni, Asha AU - Ramanunni A FAU - Mo, Xiaokui AU - Mo X FAU - Jarjoura, David AU - Jarjoura D FAU - Byrd, John C AU - Byrd JC FAU - Heerema, Nyla A AU - Heerema NA LA - eng GR - P01 CA95426/CA/NCI NIH HHS/United States GR - P50 CA140158/CA/NCI NIH HHS/United States GR - 1K12 CA133250/CA/NCI NIH HHS/United States GR - P01 CA101956/CA/NCI NIH HHS/United States GR - P50-CA140158/CA/NCI NIH HHS/United States GR - P50 CA140158-03/CA/NCI NIH HHS/United States GR - P01 CA095426/CA/NCI NIH HHS/United States GR - K12 CA133250/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Cancer Genet JT - Cancer genetics JID - 101539150 RN - 0 (GNKG168) RN - 0 (Oligodeoxyribonucleotides) RN - 0 (Pokeweed Mitogens) RN - NI40JAQ945 (Tetradecanoylphorbol Acetate) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - *Chromosome Aberrations MH - Humans MH - Karyotyping/*methods MH - Leukemia, Lymphocytic, Chronic, B-Cell/*diagnosis/*genetics MH - Middle Aged MH - Oligodeoxyribonucleotides MH - Pokeweed Mitogens MH - Sensitivity and Specificity MH - Tetradecanoylphorbol Acetate PMC - PMC3073597 MID - NIHMS261046 EDAT- 2011/04/16 06:00 MHDA- 2011/06/15 06:00 PMCR- 2012/02/01 CRDT- 2011/04/16 06:00 PHST- 2011/04/16 06:00 [entrez] PHST- 2011/04/16 06:00 [pubmed] PHST- 2011/06/15 06:00 [medline] PHST- 2012/02/01 00:00 [pmc-release] AID - S2210-7762(10)00604-6 [pii] AID - 10.1016/j.cancergen.2010.12.006 [doi] PST - ppublish SO - Cancer Genet. 2011 Feb;204(2):77-83. doi: 10.1016/j.cancergen.2010.12.006.