Aggressive disease defined by cytogenetics is associated with cytokine dysregulation in CLL/SLL patients

Reem Karmali, Laura A. Paganessi, Robin R. Frank, Sucheta Jagan, Melissa L. Larson, Parameswaran Venugopal, Stephanie A. Gregory, Kent W. Christopherson

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Early treatment of CLL/SLL does not impact survivalreflecting limitations in detecting progression early and identifying asymptomatic patients likely to benefit from early treatment. Improved understanding of CLL/SLL biology would identify better prognostic/predictive markers. This study attempts to address these issues by determining the relationship between cytokine aberrations and poor clinical outcomes in CLL/ SLL in the context of a genetic-based prognostic model. Fifty-nine serum cytokines/chemokines were measured in 28 untreated CLL/SLL patients. Patients were stratified as GR or int/PR using cytogenetics. Comparison of CLL/SLL with 28 HCs revealed increased expression of Th2 cytokines (IL-10, IL-5, sIL- 2Rα; P≤0.01) and decreased levels of Th1 cytokines (IL-17, IL-23, IFN-γ; P≤0.003). In a multivariate analysis of GR versus int/PR groups, differential expression of sIL-2Rα maintained significance with increased expression in int/PR CLL/SLL. With median follow-up of 54.3 months after diagnosis, four patients incurred disease progression, with an IL-17/sIL-2Rα model predicting need for treatment in all cases. In summary, specific cytokine signatures are associated with genetically defined aggressive disease and predict need for therapy. This suggests utility in detecting disease progression early, identifying those likely to incur a survival advantage with early treatment, and directing future therapy.

Original languageEnglish (US)
Pages (from-to)161-170
Number of pages10
JournalJournal of Leukocyte Biology
Volume93
Issue number1
DOIs
StatePublished - Jan 1 2013

Keywords

  • B-cell lymphoma
  • Genetic profile
  • sIL-2Rα
  • Th1
  • Th2

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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