IGHV3-21 Gene Frequency in a Swedish Cohort of Patients With Newly Diagnosed Chronic Lymphocytic Leukemia

Nicola Cahill, Lesley-Ann Sutton, Mattias Jansson, Fiona Murray, Larry Mansouri, Rebeqa Gunnarsson, Fergus Ryan, Karin E. Smedby, Christian Geisler, Gunnar Juliusson, Richard Rosenquist

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10 Citations (SciVal)

Abstract

The IGHV3-21 gene has been shown to be overrepresented in Scandinavian patients with chronic lymphocytic leukemia (CLL). By investigating a population-based cohort of 337 Swedish patients with CLL, a lower (6.5%) IGHV3-21 frequency was determined relative to our previous hospital-based studies (10.1%-12.7%), yet this frequency remained higher compared to other Western CLL cohorts (2.6%-4.1%). Furthermore, we confirmed the poor outcome for patients with IGHV3-21 to be independent of mutational and stereotypy status. Background: Scandinavian patients with CLL have shown an overrepresentation of the poor-prognostic IGHV3-21 gene. Furthermore, approximately 50% of patients with IGHV3-21 carry stereotyped B-cell receptors, which implicate antigen selection in leukemogenesis. These patients have also been reported to have shorter time to progression than patients with nonstereotyped IGHV3-21. Materials and Methods: To investigate the IGHV3-21 frequency and the clinical impact of IGHV3-21 stereotypy, 337 newly diagnosed Swedish CLL patients from a population-based cohort were analyzed. Results: Interestingly, the IGHV3-21 frequency was indeed lower (6.5%) in this indolent patient cohort than in our previous hospital-based cohort studies (10.1%-12.7%). Hence, a selection bias of more-aggressive cases rendered a higher proportion of IGHV3-21 cases in our original studies. Nevertheless, the Swedish IGHV3-21 frequency still remained higher when compared with other larger European or American studies (2.6%-4.1%). Finally, we confirmed the poor outcome for IGHV3-21 patients to be independent of mutational status and found stereotypy to have no impact on survival or time to treatment. Conclusion: The Swedish geographic bias in IGHV3-21 gene frequency was validated albeit at a lower frequency than previously reported. Moreover, no prognostic value could be attributed to IGHV3-21 stereotype status. Clinical Lymphoma, Myeloma & Leukemia, Vol. 12, No. 3, 201-6 (C) 2012 Elsevier Inc. All rights reserved.
Original languageEnglish
Pages (from-to)201-206
JournalClinical Lymphoma, Myeloma & Leukemia
Volume12
Issue number3
DOIs
Publication statusPublished - 2012

Subject classification (UKÄ)

  • Cancer and Oncology

Keywords

  • Chronic lymphocytic leukemia
  • Immunoglobulin heavy-chain variable 3 21
  • gene frequency
  • Prognosis
  • Stereotyped B-cell receptors

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