Home > Publications database > Validation of ZAP-70 methylation and its relative significance in predicting outcome in chronic lymphocytic leukemia. > print |
001 | 119761 | ||
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024 | 7 | _ | |a 10.1182/blood-2014-02-555722 |2 doi |
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024 | 7 | _ | |a 1528-0020 |2 ISSN |
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037 | _ | _ | |a DKFZ-2017-00388 |
041 | _ | _ | |a eng |
082 | _ | _ | |a 610 |
100 | 1 | _ | |a Claus, Rainer |0 P:(DE-HGF)0 |b 0 |e First author |
245 | _ | _ | |a Validation of ZAP-70 methylation and its relative significance in predicting outcome in chronic lymphocytic leukemia. |
260 | _ | _ | |a Stanford, Calif. |c 2014 |b HighWire Press |
336 | 7 | _ | |a article |2 DRIVER |
336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1488967355_17423 |2 PUB:(DE-HGF) |
336 | 7 | _ | |a ARTICLE |2 BibTeX |
336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
520 | _ | _ | |a ZAP-70 methylation 223 nucleotides downstream of transcription start (CpG+223) predicts outcome in chronic lymphocytic leukemia (CLL), but its impact relative to CD38 and ZAP-70 expression or immunoglobulin heavy chain variable region (IGHV) status is uncertain. Additionally, standardizing ZAP-70 expression analysis has been unsuccessful. CpG+223 methylation was quantitatively determined in 295 untreated CLL cases using MassARRAY. Impact on clinical outcome vs CD38 and ZAP-70 expression and IGHV status was evaluated. Cases with low methylation (<20%) had significantly shortened time to first treatment (TT) and overall survival (OS) (P < .0001). For TT, low methylation defined a large subset of ZAP-70 protein-negative cases with significantly shortened TT (median, 8.0 vs 3.9 years for high vs low methylation; hazard ratio [HR] = 0.43; 95% confidence interval [CI], 0.25-0.74). Conversely, 16 ZAP-70 protein-positive cases with high methylation had poor outcome (median, 1.1 vs 2.3 years for high vs low methylation; HR = 1.62; 95% CI, 0.87-3.03). For OS, ZAP-70 methylation was the strongest risk factor; CD38 and ZAP-70 expression or IGHV status did not significantly improve OS prediction. A pyrosequencing assay was established that reproduced the MassARRAY data (κ coefficient > 0.90). Thus, ZAP-70 CpG+223 methylation represents a superior biomarker for TT and OS that can be feasibly measured, supporting its use in risk-stratifying CLL. |
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588 | _ | _ | |a Dataset connected to CrossRef, PubMed, |
650 | _ | 7 | |a Biomarkers, Tumor |2 NLM Chemicals |
650 | _ | 7 | |a Immunoglobulin Variable Region |2 NLM Chemicals |
650 | _ | 7 | |a ZAP-70 Protein-Tyrosine Kinase |0 EC 2.7.10.2 |2 NLM Chemicals |
650 | _ | 7 | |a ZAP70 protein, human |0 EC 2.7.10.2 |2 NLM Chemicals |
700 | 1 | _ | |a Lucas, David M |b 1 |
700 | 1 | _ | |a Ruppert, Amy S |b 2 |
700 | 1 | _ | |a Williams, Katie E |b 3 |
700 | 1 | _ | |a Weng, Daniel |b 4 |
700 | 1 | _ | |a Patterson, Kara |b 5 |
700 | 1 | _ | |a Zucknick, Manuela |0 P:(DE-HGF)0 |b 6 |
700 | 1 | _ | |a Oakes, Christopher C |0 P:(DE-HGF)0 |b 7 |
700 | 1 | _ | |a Rassenti, Laura Z |b 8 |
700 | 1 | _ | |a Greaves, Andrew W |b 9 |
700 | 1 | _ | |a Geyer, Susan |b 10 |
700 | 1 | _ | |a Wierda, William G |b 11 |
700 | 1 | _ | |a Brown, Jennifer R |b 12 |
700 | 1 | _ | |a Gribben, John G |b 13 |
700 | 1 | _ | |a Barrientos, Jacqueline C |b 14 |
700 | 1 | _ | |a Rai, Kanti R |b 15 |
700 | 1 | _ | |a Kay, Neil E |b 16 |
700 | 1 | _ | |a Kipps, Thomas J |b 17 |
700 | 1 | _ | |a Shields, Peter |b 18 |
700 | 1 | _ | |a Zhao, Weiqiang |b 19 |
700 | 1 | _ | |a Grever, Michael R |b 20 |
700 | 1 | _ | |a Plass, Christoph |0 P:(DE-He78)4301875630bc997edf491c694ae1f8a9 |b 21 |u dkfz |
700 | 1 | _ | |a Byrd, John C |b 22 |
773 | _ | _ | |a 10.1182/blood-2014-02-555722 |g Vol. 124, no. 1, p. 42 - 48 |0 PERI:(DE-600)1468538-3 |n 1 |p 42 - 48 |t Blood |v 124 |y 2014 |x 1528-0020 |
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