Recurrent mutations refine prognosis in chronic lymphocytic leukemia
2014; Springer Nature; Volume: 29; Issue: 2 Linguagem: Inglês
10.1038/leu.2014.196
ISSN1476-5551
AutoresPanagiotis Baliakas, Anastasia Hadzidimitriou, L-A Sutton, Davide Rossi, Eva Minga, Neus Villamor, Marta Larráyoz, Jana Kmínková, Andreas Agathangelidis, Zadie Davis, Eugen Tausch, Evangelia Stalika, Barbara Kantorová, Larry Mansouri, Lydia Scarfò, Diego Cortese, Veronika Navrkalová, Matthew Rose‐Zerilli, Karin E. Smedby, Gunnar Juliusson, Αchilles Anagnostopoulos, Antonis Makris, Alba Navarro, Julio Delgado, David Oscier, Chrysoula Belessi, Stephan Stilgenbauer, Paolo Ghia, Šárka Pospı́šilová, Gianluca Gaïdano, Elı́as Campo, Jonathan C. Strefford, Κώστας Σταματόπουλος, Richard Rosenquist,
Tópico(s)Immunodeficiency and Autoimmune Disorders
ResumoThrough the European Research Initiative on chronic lymphocytic leukemia (CLL) (ERIC), we screened 3490 patients with CLL for mutations within the NOTCH1 (n=3334), SF3B1 (n=2322), TP53 (n=2309), MYD88 (n=1080) and BIRC3 (n=919) genes, mainly at diagnosis (75%) and before treatment (>90%). BIRC3 mutations (2.5%) were associated with unmutated IGHV genes (U-CLL), del(11q) and trisomy 12, whereas MYD88 mutations (2.2%) were exclusively found among M-CLL. NOTCH1, SF3B1 and TP53 exhibited variable frequencies and were mostly enriched within clinically aggressive cases. Interestingly, as the timespan between diagnosis and mutational screening increased, so too did the incidence of SF3B1 mutations; no such increase was observed for NOTCH1 mutations. Regarding the clinical impact, NOTCH1 mutations, SF3B1 mutations and TP53 aberrations (deletion/mutation, TP53ab) correlated with shorter time-to-first-treatment (P<0.0001) in 889 treatment-naive Binet stage A cases. In multivariate analysis (n=774), SF3B1 mutations and TP53ab along with del(11q) and U-CLL, but not NOTCH1 mutations, retained independent significance. Importantly, TP53ab and SF3B1 mutations had an adverse impact even in U-CLL. In conclusion, we support the clinical relevance of novel recurrent mutations in CLL, highlighting the adverse impact of SF3B1 and TP53 mutations, even independent of IGHV mutational status, thus underscoring the need for urgent standardization/harmonization of the detection methods.
Referência(s)