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

Two main genetic pathways lead to the transformation of chronic lymphocytic leukemia to Richter Syndrome
Two main genetic pathways lead to the transformation of chronic lymphocytic leukemia to Richter Syndrome
Richter syndrome (RS) occurs in up to 15% of patients with chronic lymphocytic leukemia (CLL). While 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 pre-existing CLL, mechanisms leading to RS have not been clarified yet. 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 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. While 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 when compared with untransformed CLL, but it presented clear differences in the frequency of specific genetic lesions.
0006-4971
Chigrinova, Ekaterina
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Rinaldi, Andrea
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Kwee, Ivo
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Rossi, Davide
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Rancoita, Paola M.V.
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Strefford, Jonathan C.
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Oscier, David
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Stamatopoulos, Kostas
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Papadaki, Theodora
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Berger, Francoise
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Young, Ken H.
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Murray, Fiona
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Rosenquist, Richard
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Greiner, Timothy C.
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Chan, Wing C.
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Orlandi, Ester M.
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Lucioni, Marco
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Marasca, Roberto
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Inghirami, Giorgio
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Ladetto, Marco
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Forconi, Francesco
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Cogliatti, Sergio
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Votavova, Hana
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Swerdlow, Steven H.
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Stilgenbauer, Stephan
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Piris, Miguel A.
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Matolcsy, Andras
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Spagnolo, Dominic
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Nikitin, Eugene
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Zamò, Alberto
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Gattei, Valter
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Bhagat, Govind
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Zucca, Emanuele
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Gaidano, Gianluca
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Bertoni, Francesco
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Chigrinova, Ekaterina
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Rinaldi, Andrea
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Kwee, Ivo
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Rossi, Davide
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Rancoita, Paola M.V.
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Strefford, Jonathan C.
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Stamatopoulos, Kostas
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Berger, Francoise
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Young, Ken H.
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Murray, Fiona
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Rosenquist, Richard
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Greiner, Timothy C.
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Chan, Wing C.
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Orlandi, Ester M.
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Lucioni, Marco
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Marasca, Roberto
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Inghirami, Giorgio
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Ladetto, Marco
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Forconi, Francesco
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Cogliatti, Sergio
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Votavova, Hana
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Swerdlow, Steven H.
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Stilgenbauer, Stephan
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Piris, Miguel A.
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Matolcsy, Andras
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Spagnolo, Dominic
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Nikitin, Eugene
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Zamò, Alberto
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Gattei, Valter
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Bhagat, Govind
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Zucca, Emanuele
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Gaidano, Gianluca
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Bertoni, Francesco
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Chigrinova, Ekaterina, Rinaldi, Andrea, Kwee, Ivo, Rossi, Davide, Rancoita, Paola M.V., Strefford, Jonathan C., Oscier, David, Stamatopoulos, Kostas, Papadaki, Theodora, Berger, Francoise, Young, Ken H., Murray, Fiona, Rosenquist, Richard, Greiner, Timothy C., Chan, Wing C., Orlandi, Ester M., Lucioni, Marco, Marasca, Roberto, Inghirami, Giorgio, Ladetto, Marco, Forconi, Francesco, Cogliatti, Sergio, Votavova, Hana, Swerdlow, Steven H., Stilgenbauer, Stephan, Piris, Miguel A., Matolcsy, Andras, Spagnolo, Dominic, Nikitin, Eugene, Zamò, Alberto, Gattei, Valter, Bhagat, Govind, Ott, German, Zucca, Emanuele, Gaidano, Gianluca and Bertoni, Francesco (2013) Two main genetic pathways lead to the transformation of chronic lymphocytic leukemia to Richter Syndrome. Blood. (doi:10.1182/blood-2013-03-489518). (PMID:24004666)

Record type: Article

Abstract

Richter syndrome (RS) occurs in up to 15% of patients with chronic lymphocytic leukemia (CLL). While 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 pre-existing CLL, mechanisms leading to RS have not been clarified yet. 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 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. While 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 when compared with untransformed CLL, but it presented clear differences in the frequency of specific genetic lesions.

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More information

e-pub ahead of print date: 4 September 2013
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 358096
URI: https://eprints.soton.ac.uk/id/eprint/358096
ISSN: 0006-4971
PURE UUID: 71caacb0-da2f-4bbf-967d-23b9579843b5
ORCID for Jonathan C. Strefford: ORCID iD orcid.org/0000-0002-0972-2881

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Date deposited: 04 Oct 2013 08:46
Last modified: 06 Jun 2018 12:43

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Contributors

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

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