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Recurrent mutations refine prognosis in chronic lymphocytic leukemia.

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BALIAKAS P. HADZIDIMITRIOU A. SUTTON LA. ROSSI D. MINGA E. VILLAMOR N. LARRAYOZ M. KMÍNKOVÁ Jana AGATHANGELIDIS A. DAVIS Z. TAUSCH E. STALIKA E. KANTOROVÁ Barbara MANSOURI L. SCARFO L. CORTESE D. NAVRKALOVÁ Veronika ROSE-ZERILLI MJ. SMEDBY K.E. JULIUSSON G. ANAGNOSTOPOULOS A. MAKRIS A.M. NAVARRO A. DELGADO J. OSCIER D. BELESSI C. STILGENBAUER S. GHIA P. POSPÍŠILOVÁ Šárka GAIDANO G. CAMPO E. STREFFORD J.C. STAMATOPOULOS K. ROSENQUIST R.

Rok publikování 2015
Druh Článek v odborném periodiku
Časopis / Zdroj Leukemia
Fakulta / Pracoviště MU

Středoevropský technologický institut

Citace
www http://www.nature.com/leu/journal/vaop/ncurrent/pdf/leu2014196a.pdf
Doi http://dx.doi.org/10.1038/leu.2014.196
Obor Onkologie a hematologie
Klíčová slova mutations; CLL; ERIC
Přiložené soubory
Popis Through the European Research Initiative on chronic lymphocytic leukemia (CLL) (ERIC), we screened 3490 patients with CLL for mutations within the NOTCH1 (n 1/4 3334), SF3B1 (n 1/4 2322), TP53 (n 1/4 2309), MYD88 (n 1/4 1080) and BIRC3 (n 1/4 919) genes, mainly at diagnosis (75%) and before treatment (490%). 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 (Po0.0001) in 889 treatment-naive Binet stage A cases. In multivariate analysis (n 1/4 774), 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.
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