title: Two main genetic pathways lead to the transformation of chronic lymphocytic leukemia to Richter syndrome.
abstract: 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.
authors.affiliation: Lymphoma and Genomics Research Program, IOR Institute of Oncology Research, Bellinzona, Switzerland;
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Chigrinova
authors.forename: Andrea
authors.initials: A
authors.lastname: Rinaldi
authors.forename: Ivo
authors.initials: I
authors.lastname: Kwee
authors.forename: Davide
authors.initials: D
authors.lastname: Rossi
authors.forename: Paola M V
authors.initials: PM
authors.lastname: Rancoita
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Strefford
authors.forename: David
authors.initials: D
authors.lastname: Oscier
authors.forename: Kostas
authors.initials: K
authors.lastname: Stamatopoulos
authors.forename: Theodora
authors.initials: T
authors.lastname: Papadaki
authors.forename: Francoise
authors.initials: F
authors.lastname: Berger
authors.forename: Ken H
authors.initials: KH
authors.lastname: Young
authors.forename: Fiona
authors.initials: F
authors.lastname: Murray
authors.forename: Richard
authors.initials: R
authors.lastname: Rosenquist
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Greiner
authors.forename: Wing C
authors.initials: WC
authors.lastname: Chan
authors.forename: Ester M
authors.initials: EM
authors.lastname: Orlandi
authors.forename: Marco
authors.initials: M
authors.lastname: Lucioni
authors.forename: Roberto
authors.initials: R
authors.lastname: Marasca
authors.forename: Giorgio
authors.initials: G
authors.lastname: Inghirami
authors.forename: Marco
authors.initials: M
authors.lastname: Ladetto
authors.forename: Francesco
authors.initials: F
authors.lastname: Forconi
authors.forename: Sergio
authors.initials: S
authors.lastname: Cogliatti
authors.forename: Hana
authors.initials: H
authors.lastname: Votavova
authors.forename: Steven H
authors.initials: SH
authors.lastname: Swerdlow
authors.forename: Stephan
authors.initials: S
authors.lastname: Stilgenbauer
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Piris
authors.forename: Andras
authors.initials: A
authors.lastname: Matolcsy
authors.forename: Dominic
authors.initials: D
authors.lastname: Spagnolo
authors.forename: Eugene
authors.initials: E
authors.lastname: Nikitin
authors.forename: Alberto
authors.initials: A
authors.lastname: Zamò
authors.forename: Valter
authors.initials: V
authors.lastname: Gattei
authors.forename: Govind
authors.initials: G
authors.lastname: Bhagat
authors.forename: German
authors.initials: G
authors.lastname: Ott
authors.forename: Emanuele
authors.initials: E
authors.lastname: Zucca
authors.forename: Gianluca
authors.initials: G
authors.lastname: Gaidano
authors.forename: Francesco
authors.initials: F
authors.lastname: Bertoni
mesh_terms: D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D018450:Disease Progression; D005260:Female; D015973:Gene Expression Regulation, Leukemic / Q000235:genetics*; D019942:Genes, p16 / Q000502:physiology; D055106:Genome-Wide Association Study; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D014314:Trisomy / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53