BACKGROUND: Chromosomal abnormalities and gene mutations determine the prognosis of patients with chronic lymphocytic leukemia (CLL). Genetic lesions can be acquired by clonal evolution (CE) likely correlating with clinical progression. METHODS AND RESULTS: Samples of 169 CLL patients were analyzed for cytogenetic clonal evolution (CCE) and CE affecting the genes TP53 and SF3B1. Moreover, the mutational status of IGHV and the clinical outcome was evaluated. CCE was observed in 35% of CLL patients. The most frequently gained cytogenetic aberration was a deletion of TP53. Acquired TP53 deletion was more frequent in patients with SF3B1 mutations compared to those without (19% vs. 7%). CCE showed a tendency to occur more frequently in patients with an aberrant karyotype at first investigation than in patients with a normal karyotype. In 73% of patients with CCE (p = 0.002) and 92% of patients with CE affecting the genes TP53 and SF3B1 (p < 0.001) an unmutated IGHV status was present. CCE and CE affecting the genes TP53 and SF3B1 were significantly associated with each other (p < 0.001). In 7% of patients, CE resulted in the co-occurrence of TP53 deletion and TP53 mutation resulting in a significantly shorter overall survival. CONCLUSIONS: The most frequently gained cytogenetic aberration during CCE was a deletion of TP53, which was associated with SF3B1 mutations. Moreover, CCE was associated with an unmutated IGHV status. Our results indicate the importance of re-evaluation of the TP53 status during the course of the disease to ensure correct treatment guidance.
BACKGROUND: Chromosomal abnormalities and gene mutations determine the prognosis of patients with chronic lymphocytic leukemia (CLL). Genetic lesions can be acquired by clonal evolution (CE) likely correlating with clinical progression. METHODS AND RESULTS: Samples of 169 CLL patients were analyzed for cytogenetic clonal evolution (CCE) and CE affecting the genes TP53 and SF3B1. Moreover, the mutational status of IGHV and the clinical outcome was evaluated. CCE was observed in 35% of CLL patients. The most frequently gained cytogenetic aberration was a deletion of TP53. Acquired TP53 deletion was more frequent in patients with SF3B1 mutations compared to those without (19% vs. 7%). CCE showed a tendency to occur more frequently in patients with an aberrant karyotype at first investigation than in patients with a normal karyotype. In 73% of patients with CCE (p = 0.002) and 92% of patients with CE affecting the genes TP53 and SF3B1 (p < 0.001) an unmutated IGHV status was present. CCE and CE affecting the genes TP53 and SF3B1 were significantly associated with each other (p < 0.001). In 7% of patients, CE resulted in the co-occurrence of TP53 deletion and TP53 mutation resulting in a significantly shorter overall survival. CONCLUSIONS: The most frequently gained cytogenetic aberration during CCE was a deletion of TP53, which was associated with SF3B1 mutations. Moreover, CCE was associated with an unmutated IGHV status. Our results indicate the importance of re-evaluation of the TP53 status during the course of the disease to ensure correct treatment guidance.
Authors: Stephan Stilgenbauer; Andrea Schnaiter; Peter Paschka; Thorsten Zenz; Marianna Rossi; Konstanze Döhner; Andreas Bühler; Sebastian Böttcher; Matthias Ritgen; Michael Kneba; Dirk Winkler; Eugen Tausch; Patrick Hoth; Jennifer Edelmann; Daniel Mertens; Lars Bullinger; Manuela Bergmann; Sabrina Kless; Silja Mack; Ulrich Jäger; Nancy Patten; Lin Wu; Michael K Wenger; Günter Fingerle-Rowson; Peter Lichter; Mario Cazzola; Clemens M Wendtner; Anna M Fink; Kirsten Fischer; Raymonde Busch; Michael Hallek; Hartmut Döhner Journal: Blood Date: 2014-03-20 Impact factor: 22.113
Authors: H Döhner; S Stilgenbauer; A Benner; E Leupolt; A Kröber; L Bullinger; K Döhner; M Bentz; P Lichter Journal: N Engl J Med Date: 2000-12-28 Impact factor: 91.245
Authors: R N Damle; T Wasil; F Fais; F Ghiotto; A Valetto; S L Allen; A Buchbinder; D Budman; K Dittmar; J Kolitz; S M Lichtman; P Schulman; V P Vinciguerra; K R Rai; M Ferrarini; N Chiorazzi Journal: Blood Date: 1999-09-15 Impact factor: 22.113
Authors: Panagiotis Baliakas; Sabine Jeromin; Michalis Iskas; Anna Puiggros; Karla Plevova; Florence Nguyen-Khac; Zadie Davis; Gian Matteo Rigolin; Andrea Visentin; Aliki Xochelli; Julio Delgado; Fanny Baran-Marszak; Evangelia Stalika; Pau Abrisqueta; Kristina Durechova; George Papaioannou; Virginie Eclache; Maria Dimou; Theodoros Iliakis; Rosa Collado; Michael Doubek; M Jose Calasanz; Neus Ruiz-Xiville; Carolina Moreno; Marie Jarosova; Alexander C Leeksma; Panayiotis Panayiotidis; Helena Podgornik; Florence Cymbalista; Achilles Anagnostopoulos; Livio Trentin; Niki Stavroyianni; Fred Davi; Paolo Ghia; Arnon P Kater; Antonio Cuneo; Sarka Pospisilova; Blanca Espinet; Anastasia Athanasiadou; David Oscier; Claudia Haferlach; Kostas Stamatopoulos Journal: Blood Date: 2019-01-02 Impact factor: 22.113
Authors: Torsten Haferlach; Claudia Schoch; Helmut Löffler; Winfried Gassmann; Wolfgang Kern; Susanne Schnittger; Christa Fonatsch; Wolf-Dieter Ludwig; Christian Wuchter; Brigitte Schlegelberger; Peter Staib; Albrecht Reichle; Uschi Kubica; Hartmut Eimermacher; Leopold Balleisen; Andreas Grüneisen; Detlef Haase; Carlo Aul; Jochen Karow; Eva Lengfelder; Bernhard Wörmann; Achim Heinecke; Maria Cristina Sauerland; Thomas Büchner; Wolfgang Hiddemann Journal: J Clin Oncol Date: 2003-01-15 Impact factor: 44.544