Two main genetic pathways lead to the transformation of chronic lymphocytic leukemia to Richter syndrome

Ekaterina Chigrinova, Andrea Rinaldi, Ivo Kwee, Davide Rossi, Paola M.V. Rancoita, Jonathan C. Strefford, David Oscier, Kostas Stamatopoulos, Theodora Papadaki, Francoise Berger, Ken H. Young, Fiona Murray, Richard Rosenquist, Timothy C. Greiner, Wing C. Chan, Ester M. Orlandi, Marco Lucioni, Roberto Marasca, Giorgio Inghirami, Marco LadettoFrancesco Forconi, Sergio Cogliatti, Hana Votavova, Steven H. Swerdlow, Stephan Stilgenbauer, Miguel A. Piris, Andras Matolcsy, Dominic Spagnolo, Eugene Nikitin, Alberto Zamò, Valter Gattei, Govind Bhagat, German Ott, Emanuele Zucca, Gianluca Gaidano, Francesco Bertoni

Research output: Contribution to journalArticlepeer-review

195 Scopus citations


Richter syndrome (RS) occurs in up to 15% of patients with chronic lymphocytic leukemia (CLL). Although RS, usually represented by the histologic transformation to a diffuse large B-cell lymphoma (DLBCL), is associated with a very poor outcome, especially when clonally related to the preexisting CLL, the mechanisms leading to RS have not been clarified. To better understand the pathogenesis of RS, we analyzed a series of cases including 59 RS, 28 CLL phase of RS, 315 CLL, and 127 de novo DLBCL. RS demonstrated a genomic complexity intermediate between CLL and DLBCL. Cell-cycle deregulation via inactivation of TP53 and of CDKN2A was a main mechanism in the histologic transformation from CLL phase, being present in approximately one half of the cases, and affected the outcome of the RS patients. A second major subgroup was characterized by the presence of trisomy 12 and comprised one third of the cases. Although RS shared some of the lesions seen in de novo DLBCL, its genomic profile was clearly separate. The CLL phase preceding RS had not a generalized increase in genomic complexity compared with untransformed CLL, but it presented clear differences in the frequency of specific genetic lesions.

Original languageEnglish (US)
Pages (from-to)2673-2682
Number of pages10
Issue number15
StatePublished - 2013

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology


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