The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Recurrent mutations refine prognosis in chronic lymphocytic leukemia.

På svenska

Author

  • P Baliakas
  • A Hadzidimitriou
  • L-A Sutton
  • D Rossi
  • E Minga
  • N Villamor
  • M Larrayoz
  • J Kminkova
  • A Agathangelidis
  • Z Davis
  • E Tausch
  • E Stalika
  • B Kantorova
  • L Mansouri
  • L Scarfò
  • D Cortese
  • V Navrkalova
  • M J J Rose-Zerilli
  • K E Smedby
  • Gunnar Juliusson
  • A Anagnostopoulos
  • A M Makris
  • A Navarro
  • J Delgado
  • D Oscier
  • C Belessi
  • S Stilgenbauer
  • P Ghia
  • S Pospisilova
  • G Gaidano
  • E Campo
  • J C Strefford
  • K Stamatopoulos
  • R Rosenquist
Show all

Summary, in English

Through the European Research Initiative in CLL (ERIC), we screened 3490 patients with chronic lymphocytic leukemia (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 prior to 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-naïve Binet 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.Leukemia accepted article preview online, 19 June 2014; doi:10.1038/leu.2014.196.

Department/s

  • Stem Cell Center
  • BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation

Publishing year

2015

Language

English

Pages

329-336

Publication/Series

Leukemia

Volume

29

Issue

2

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Cancer and Oncology

Status

Published

ISBN/ISSN/Other

  • ISSN: 1476-5551