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Genomic complexity identifies patients with aggressive chronic lymphocytic leukemia.

Publication ,  Journal Article
Kujawski, L; Ouillette, P; Erba, H; Saddler, C; Jakubowiak, A; Kaminski, M; Shedden, K; Malek, SN
Published in: Blood
September 1, 2008

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.

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Published In

Blood

DOI

EISSN

1528-0020

Publication Date

September 1, 2008

Volume

112

Issue

5

Start / End Page

1993 / 2003

Location

United States

Related Subject Headings

  • ZAP-70 Protein-Tyrosine Kinase
  • Time Factors
  • Prospective Studies
  • Prognosis
  • Polymorphism, Single Nucleotide
  • Mutation
  • Multivariate Analysis
  • Middle Aged
  • Membrane Glycoproteins
  • Male
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Kujawski, L., Ouillette, P., Erba, H., Saddler, C., Jakubowiak, A., Kaminski, M., … Malek, S. N. (2008). Genomic complexity identifies patients with aggressive chronic lymphocytic leukemia. Blood, 112(5), 1993–2003. https://doi.org/10.1182/blood-2007-07-099432
Kujawski, Lisa, Peter Ouillette, Harry Erba, Chris Saddler, Andrzej Jakubowiak, Mark Kaminski, Kerby Shedden, and Sami N. Malek. “Genomic complexity identifies patients with aggressive chronic lymphocytic leukemia.Blood 112, no. 5 (September 1, 2008): 1993–2003. https://doi.org/10.1182/blood-2007-07-099432.
Kujawski L, Ouillette P, Erba H, Saddler C, Jakubowiak A, Kaminski M, et al. Genomic complexity identifies patients with aggressive chronic lymphocytic leukemia. Blood. 2008 Sep 1;112(5):1993–2003.
Kujawski, Lisa, et al. “Genomic complexity identifies patients with aggressive chronic lymphocytic leukemia.Blood, vol. 112, no. 5, Sept. 2008, pp. 1993–2003. Pubmed, doi:10.1182/blood-2007-07-099432.
Kujawski L, Ouillette P, Erba H, Saddler C, Jakubowiak A, Kaminski M, Shedden K, Malek SN. Genomic complexity identifies patients with aggressive chronic lymphocytic leukemia. Blood. 2008 Sep 1;112(5):1993–2003.

Published In

Blood

DOI

EISSN

1528-0020

Publication Date

September 1, 2008

Volume

112

Issue

5

Start / End Page

1993 / 2003

Location

United States

Related Subject Headings

  • ZAP-70 Protein-Tyrosine Kinase
  • Time Factors
  • Prospective Studies
  • Prognosis
  • Polymorphism, Single Nucleotide
  • Mutation
  • Multivariate Analysis
  • Middle Aged
  • Membrane Glycoproteins
  • Male