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

Publication

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

Journal Paper/Review - Sep 4, 2013

Chigrinova Ekaterina, Ladetto Marco, Forconi Francesco, Cogliatti Sergio B., 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, Inghirami Giorgio, Marasca Roberto, Rinaldi Andrea, Kwee Ivo, Rossi Davide, Rancoita Paola M V, Strefford Jonathan C, Oscier David, Stamatopoulos Kostas, Papadaki Theodora, Berger Françoise, Young Ken H, Murray Fiona, Rosenquist Richard, Greiner Timothy C, Chan Wing C, Orlandi Ester M, Lucioni Marco, Bertoni Francesco

Citation

Chigrinova E, Ladetto M, Forconi F, Cogliatti S, Votavova H, Swerdlow S, Stilgenbauer S, Piris M, Matolcsy A, Spagnolo D, Nikitin E, Zamò A, Gattei V, Bhagat G, Ott G, Zucca E, Gaidano G, Inghirami G, Marasca R, Rinaldi A, Kwee I, Rossi D, Rancoita P, Strefford J, Oscier D, Stamatopoulos K, Papadaki T, Berger F, Young K, Murray F, Rosenquist R, Greiner T, Chan W, Orlandi E, Lucioni M, Bertoni F. Two main genetic pathways lead to the transformation of chronic lymphocytic leukemia to Richter syndrome. Blood 2013; 122:2673-82.

Type

Journal Paper/Review (English)

Journal

Blood 2013; 122

Publication Date

Sep 4, 2013

Issn Electronic

1528-0020

Pages

2673-82

Brief description/objective

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.