title: IGHV3-21 gene frequency in a Swedish cohort of patients with newly diagnosed chronic lymphocytic leukemia.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden; Department of Biological Sciences, Institute of Technology, Dublin, Ireland.
authors.forename: Nicola
authors.initials: N
authors.lastname: Cahill
authors.forename: Lesley-Ann
authors.initials: LA
authors.lastname: Sutton
authors.forename: Mattias
authors.initials: M
authors.lastname: Jansson
authors.forename: Fiona
authors.initials: F
authors.lastname: Murray
authors.forename: Larry
authors.initials: L
authors.lastname: Mansouri
authors.forename: Rebeqa
authors.initials: R
authors.lastname: Gunnarsson
authors.forename: Fergus
authors.initials: F
authors.lastname: Ryan
authors.forename: Karin E
authors.initials: KE
authors.lastname: Smedby
authors.forename: Christian
authors.initials: C
authors.lastname: Geisler
authors.forename: Gunnar
authors.initials: G
authors.lastname: Juliusson
authors.forename: Richard
authors.initials: R
authors.lastname: Rosenquist
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D011379:Prognosis; D013548:Sweden; D044465:White People
chemical_list: D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region