The genetics of Richter syndrome reveals disease heterogeneity and predicts survival after transformation

Davide Rossi, Valeria Spina, Clara Deambrogi, Silvia Rasi, Luca Laurenti, Kostas Stamatopoulos, Luca Arcaini, Marco Lucioni, Gabrielle B. Rocque, Zijun Y. Xu-Monette, Carlo Visco, Julie Chang, Ekaterina Chigrinova, Francesco Forconi, Roberto Marasca, Caroline Besson, Theodora Papadaki, Marco Paulli, Luigi M. Larocca, Stefano A. PileriValter Gattei, Francesco Bertoni, Robin Foà, Ken H. Young, Gianluca Gaidano

Research output: Contribution to journalArticle

Abstract

Richter syndrome (RS) represents the development of diffuse large B-cell lymphoma in the context of chronic lymphocytic leukemia. The scarcity of biologic information about RS has hampered the identification of molecular predictors of RS outcome. We addressed this issue by performing a comprehensive molecular characterization of 86 pathologically proven RS. TP53 disruption (47.1%) and c-MYC abnormalities (26.2%) were the most frequent alterations, whereas common genetic lesions of de novo diffuse large B-cell lymphoma were rare or absent. By multivariate analysis, lack of TP53 disruption (hazard ratio, 0.43; P = .003) translated into significant survival advantage with 57% reduction in risk of death. An algorithm based on TP53 disruption, response to RS treatment, and Eastern Cooperative Oncology Group performance status had 80.9% probability of correctly discriminating RS survival (c-index = .809). RS that were clonally unrelated to the paired chronic lymphocytic leukemia phase were clinically and biologically different from clonally related RS because of significantly longer survival (median, 62.5 months vs 14.2 months; P = .017) and lower prevalence of TP53 disruption (23.1% vs 60.0%; P = .018) and B-cell receptor stereotypy (7.6% vs 50.0%; P = .009). The molecular dissection of RS into biologically distinct categories highlights the genetic heterogeneity of this disorder and provides clinically relevant information for refining the prognostic stratification of patients.

Original languageEnglish
Pages (from-to)3391-3401
Number of pages11
JournalBlood
Volume117
Issue number12
DOIs
Publication statusPublished - Mar 24 2011

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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  • Cite this

    Rossi, D., Spina, V., Deambrogi, C., Rasi, S., Laurenti, L., Stamatopoulos, K., Arcaini, L., Lucioni, M., Rocque, G. B., Xu-Monette, Z. Y., Visco, C., Chang, J., Chigrinova, E., Forconi, F., Marasca, R., Besson, C., Papadaki, T., Paulli, M., Larocca, L. M., ... Gaidano, G. (2011). The genetics of Richter syndrome reveals disease heterogeneity and predicts survival after transformation. Blood, 117(12), 3391-3401. https://doi.org/10.1182/blood-2010-09-302174