Genomic complexity identifies patients with aggressive chronic lymphocytic leukemia.

Published

Journal Article

Chronic lymphocytic leukemia (CLL) has a variable clinical course. Presence of specific genomic aberrations has been shown to impact survival outcomes and can help categorize CLL into clinically distinct subtypes. We studied 178 CLL patients enrolled in a prospective study at the University of Michigan, of whom 139 and 39 were previously untreated and previously treated, respectively. We obtained unbiased, high-density, genome-wide measurements of subchromosomal copy number changes in highly purified DNA from sorted CD19(+) cells and buccal cells using the Affymetrix 50kXbaI SNP array platform (Santa Clara, CA). Genomic complexity scores were derived and correlated with the surrogate clinical end points time to first therapy (TTFT) and time to subsequent therapy (TTST): measures of disease aggressiveness and/or therapy efficaciousness. In univariate analysis, progressively increasing complexity scores in previously untreated CLL patients identified patients with short TTFT at high significance levels. Similarly, TTST was significantly shorter in pretreated patients with high as opposed to low genomic complexity. In multivariate analysis, genomic complexity emerged as an independent risk factor for short TTFT and TTST. Finally, algorithmic subchromosomal complexity determination was developed, facilitating automation and future routine clinical application of CLL whole-genome analysis.

Full Text

Duke Authors

Cited Authors

  • Kujawski, L; Ouillette, P; Erba, H; Saddler, C; Jakubowiak, A; Kaminski, M; Shedden, K; Malek, SN

Published Date

  • September 1, 2008

Published In

Volume / Issue

  • 112 / 5

Start / End Page

  • 1993 - 2003

PubMed ID

  • 18436738

Pubmed Central ID

  • 18436738

Electronic International Standard Serial Number (EISSN)

  • 1528-0020

Digital Object Identifier (DOI)

  • 10.1182/blood-2007-07-099432

Language

  • eng

Conference Location

  • United States