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

Cahill, Nicola; Sutton, Lesley-Ann; Jansson, Mattias; Murray, Fiona; Mansouri, Larry; Gunnarsson, Rebeqa; Ryan, Fergus; Smedby, Karin E.; Geisler, Christian and Juliusson, Gunnar LU , et al. (2012) In Clinical Lymphoma, Myeloma & Leukemia 12(3). p.201-206
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... (More)
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. (Less)
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keywords
Chronic lymphocytic leukemia, Immunoglobulin heavy-chain variable 3 21, gene frequency, Prognosis, Stereotyped B-cell receptors
in
Clinical Lymphoma, Myeloma & Leukemia
volume
12
issue
3
pages
201 - 206
publisher
CIG Media Group
external identifiers
  • wos:000304495800008
  • scopus:84861021139
ISSN
2152-2650
DOI
10.1016/j.clml.2012.01.009
language
English
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yes
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c70bfa05-5b8b-4d5e-85b0-5e27a562550f (old id 2799661)
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2012-07-03 10:25:00
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2017-01-01 03:31:38
@article{c70bfa05-5b8b-4d5e-85b0-5e27a562550f,
  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.},
  author       = {Cahill, Nicola and Sutton, Lesley-Ann and Jansson, Mattias and Murray, Fiona and Mansouri, Larry and Gunnarsson, Rebeqa and Ryan, Fergus and Smedby, Karin E. and Geisler, Christian and Juliusson, Gunnar and Rosenquist, Richard},
  issn         = {2152-2650},
  keyword      = {Chronic lymphocytic leukemia,Immunoglobulin heavy-chain variable 3 21,gene frequency,Prognosis,Stereotyped B-cell receptors},
  language     = {eng},
  number       = {3},
  pages        = {201--206},
  publisher    = {CIG Media Group},
  series       = {Clinical Lymphoma, Myeloma & Leukemia},
  title        = {IGHV3-21 Gene Frequency in a Swedish Cohort of Patients With Newly Diagnosed Chronic Lymphocytic Leukemia},
  url          = {http://dx.doi.org/10.1016/j.clml.2012.01.009},
  volume       = {12},
  year         = {2012},
}