期刊
HAEMATOLOGICA
卷 106, 期 1, 页码 87-97出版社
FERRATA STORTI FOUNDATION
DOI: 10.3324/haematol.2019.239947
关键词
-
类别
资金
- Janssen Pharmaceuticals
- GILEAD Sciences SA
- Peters van der Laan foundation
- Bloodwise [11052, 12036]
- Kay Kendall Leukaemia Fund [873]
- Cancer Research UK [C34999/A18087, ECMC C24563/A15581]
- Bournemouth Leukaemia Fund
- project MHCR DRO [65269705]
- research infrastructure NCMG [LM2015091]
- research infrastructure EATRIS-CZ [LM2015064]
- MEYS CR [CEITEC2020 LQ1601]
- Swedish Cancer Society
- Swedish Research Council
- Knut and Alice Wallenberg Foundation
- Karolinska Institutet
- Karolinska University Hospital
- Radiumhemmets Forskningsfonder, Stockholm
- Wessex Medical Research
Genomic arrays have been shown to be an accurate tool for risk stratification in CLL, with high genomic complexity being an independent adverse prognosticator. Lowering the size cutoff for CNA did not significantly improve risk assessment. Arrays detected more chromosomal abnormalities and performed at least as well as simultaneous chromosome banding analysis for risk stratification.
Complex karyotype identified by chromosome-banding analysis has been shown to have prognostic value in chronic lymphocytic leukemia (CLL). Genomic arrays offer high-resolution genomewide detection of copy-number alterations (CNA) and could therefore be well equipped to detect the presence of a complex karyotype. Current knowledge on genomic arrays in CLL is based on outcomes of single-cen ter studies, in which different cutoffs for CNA calling were used. To further determine the clinical utility of genomic arrays for CNA assessment in CLL diagnostics, we retrospectively analyzed 2,293 arrays from 13 diagnostic laboratories according to established standards. CNA were found outside regions captured by CLL fluorescence in situ hybridization probes in 34% of patients, and several of them, including gains of 8q, deletions of 9p and 18p (P<0.01), were linked to poor outcome after correction for multiple testing. Patients (n=972) could be divided into three distinct prognostic subgroups based on the number of CNA. In multivariable analysis only high genomic complexity, defined as z5 CNA, emerged as an independent adverse prognosticator for time to first treatment (hazard ratio: 2.15; 95% confidence interval: 1.36-3.41; P=0.001) and overall survival (hazard ratio: 2.54, 95% confidence interval: 1.54-4.17; P<0.001; n=528). Lowering the size cutoff to 1 Mb in 647 patients did not significantly improve risk assessment. Genomic arrays detected more chromosomal abnormalities and, in terms of risk stratification, performed at least as well as simultaneous chromosome banding analysis as carried out in 122 patients. Our findings indicate that genomic array is an accurate tool for CLL risk stratification.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据