Stereotyped B-cell receptor is an independent risk factor of chronic lymphocytic leukemia transformation to Richter syndrome.

Abstract

PURPOSE:

Few biological prognosticators are useful for prediction of Richter syndrome (RS), representing the transformation of chronic lymphocytic leukemia (CLL) to aggressive lymphoma. Stereotyped B-cell receptors (BCR) may have prognostic effect in CLL progression. We tested the prognostic effect of stereotyped BCR for predicting RS transformation.

EXPERIMENTAL DESIGN:

The prevalence of stereotyped BCR was compared in RS (n = 69) versus nontransformed CLL (n = 714) by a case-control analysis. Subsequently, the effect of stereotyped BCR at CLL diagnosis on risk of RS transformation was actuarially assessed in a consecutive CLL series (n = 753).

RESULTS:

RS (n = 69) displayed a higher prevalence of stereotyped BCR (P < 0.001) compared with nontransformed CLL. The actuarial risk of RS transformation was significantly higher in CLL carrying stereotyped BCR (P < 0.001). Among BCR subsets most represented in CLL, subset 8 using IGHV4-39/IGHD6-13/IGHJ5 carried the highest risk of RS transformation [hazard ratio (HR), 24.50; P < 0.001]. Multivariate analysis selected stereotyped BCR (HR, 3.33; P = 0.001) and IGHV4-39 usage (HR, 4.03; P = 0.004) as independent predictors of RS transformation. The combination of IGHV4-39 usage and stereotyped BCR in the same patient identified CLL with a very high risk of RS transformation (5-year risk, 68.7%). The risk carried by stereotyped BCR and IGHV4-39 usage was specific for RS transformation and had no effect on CLL progression without transformation.

CONCLUSIONS:

Analysis of BCR features may help identify CLL patients at risk of RS. A close monitoring and a careful biopsy policy may help early recognition of RS in CLL patients using stereotyped BCR, particularly if combined with IGHV4-39.

• Authors: Davide Rossi, Valeria Spina, Michaela Cerri, Silvia Rasi, Clara Deambrogi, Lorenzo De Paoli, Luca Laurenti, Rossana Maffei, Francesco Forconi, Francesco Bertoni, Emanuele Zucca, Claudio Agostinelli, Antonello Cabras, Marco Lucioni, Maurizio Martini, Michele Magni, Silvia Deaglio, Marco Ladetto, Josep F Nomdedeu, Caroline Besson, Antonio Ramponi, Vincenzo Canzonieri, Marco Paulli, Roberto Marasca, Luigi M Larocca, Antonino Carbone, Stefano A Pileri, Valter Gattei, Gianluca Gaidano
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 15 Issue 13 Pg. 4415-22 (Jul 01 2009) ISSN: 1557-3265 [Electronic] United States
• PMID: 19509140 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• BCR protein, human
• Proto-Oncogene Proteins c-bcr

Topics

• Aged
• Cohort Studies
• Disease Progression
• Female
• Gene Frequency
• Genetic Predisposition to Disease
• Humans
• Leukemia, Lymphocytic, Chronic, B-Cell (complications, genetics, pathology)
• Lymphoma (genetics, pathology)
• Male
• Middle Aged
• Neoplasm Invasiveness
• Polymorphism, Genetic (physiology)
• Proto-Oncogene Proteins c-bcr (genetics, physiology)
• Risk Factors
• Syndrome