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

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• 作者：Nicola Cahill¹ ; ² ; Lesley-Ann Sutton¹ ; Mattias Jansson¹ ; Fiona Murray¹ ; Larry Mansouri¹ ; Rebeqa Gunnarsson¹ ; Fergus Ryan² ; Karin E. Smedby³ ; Christian Geisler⁴ ; Gunnar Juliusson⁵ ; Richard Rosenquist¹ ; ^{richard.rosenquist@igp.uu.se}
• 关键词：Chronic lymphocytic leukemia ; Immunoglobulin heavy-chain variable 3 21 gene frequency ; Prognosis ; Stereotyped B-cell receptors
• 刊名：Clinical Lymphoma Myeloma and Leukemia
• 出版年：2012
• 期刊代码：pca95_21522650
• 类别：med
• 出版时间：June, 2012
• 卷：12
• 期：3
• 页码：201-206
• 文件大小：410 K

摘要

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.