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  • Mansouri, LKarolinska Institutet,Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden. (author)

Different prognostic impact of recurrent gene mutations in chronic lymphocytic leukemia depending on IGHV gene somatic hypermutation status: a study by ERIC in HARMONY

  • Article/chapterEnglish2023

Publisher, publication year, extent ...

  • 2022-12-24
  • Springer Science and Business Media LLC,2023

Numbers

  • LIBRIS-ID:oai:prod.swepub.kib.ki.se:151836592
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:151836592URI
  • https://doi.org/10.1038/s41375-022-01802-yDOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-524534URI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Recent evidence suggests that the prognostic impact of gene mutations in patients with chronic lymphocytic leukemia (CLL) may differ depending on the immunoglobulin heavy variable (IGHV) gene somatic hypermutation (SHM) status. In this study, we assessed the impact of nine recurrently mutated genes (BIRC3, EGR2, MYD88, NFKBIE, NOTCH1, POT1, SF3B1, TP53, and XPO1) in pre-treatment samples from 4580 patients with CLL, using time-to-first-treatment (TTFT) as the primary end-point in relation to IGHV gene SHM status. Mutations were detected in 1588 (34.7%) patients at frequencies ranging from 2.3–9.8% with mutations in NOTCH1 being the most frequent. In both univariate and multivariate analyses, mutations in all genes except MYD88 were associated with a significantly shorter TTFT. In multivariate analysis of Binet stage A patients, performed separately for IGHV-mutated (M-CLL) and unmutated CLL (U-CLL), a different spectrum of gene alterations independently predicted short TTFT within the two subgroups. While SF3B1 and XPO1 mutations were independent prognostic variables in both U-CLL and M-CLL, TP53, BIRC3 and EGR2 aberrations were significant predictors only in U-CLL, and NOTCH1 and NFKBIE only in M-CLL. Our findings underscore the need for a compartmentalized approach to identify high-risk patients, particularly among M-CLL patients, with potential implications for stratified management.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Thorvaldsdottir, BKarolinska Institutet,Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden. (author)
  • Sutton, LAKarolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden. (author)
  • Karakatsoulis, GInst Appl Biosci, Ctr Res & Technol Hellas, Thessaloniki, Greece.;Univ Ioannina, Dept Math, Ioannina, Greece. (author)
  • Meggendorfer, MMLL Munich Leukemia Lab, Munich, Germany. (author)
  • Parker, HUniv Southampton, Fac Med, Sch Canc Sci, Canc Genom, Southampton, England. (author)
  • Nadeu, FInst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain.;Ctr Invest Biomeed Red Canc CIBERONC, Madrid, Spain.,Sorbonne Univ, Hop Pitie Salpetriere, AP HP, Serv Hematol Clin, Paris, France. (author)
  • Brieghel, CCopenhagen Univ Hosp, Rigshosp, Dept Hematol, Copenhagen, Denmark. (author)
  • Laidou, SInst Appl Biosci, Ctr Res & Technol Hellas, Thessaloniki, Greece. (author)
  • Moia, RUniv Piemonte Orientale, Dept Translat Med, Div Hematol, Novara, Italy. (author)
  • Rossi, DOncol Inst Southern Switzerland, Div Hematol, Bellinzona, Switzerland.;Inst Oncol Res, Lab Expt Hematol, Bellinzona, Switzerland. (author)
  • Catherwood, MQueens Univ Belfast, Patrick G Johnston Ctr Canc Res, Belfast, Antrim, North Ireland. (author)
  • Kotaskova, JUniv Hosp Brno, Dept Internal Med Hematol & Oncol, Brno, Czech Republic.;Masaryk Univ, Fac Med, Brno, Czech Republic.;Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic. (author)
  • Delgado, JInst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain.;Ctr Invest Biomeed Red Canc CIBERONC, Madrid, Spain.;Hosp Clin Barcelona, Barcelona, Spain.;Univ Barcelona, Barcelona, Spain. (author)
  • Rodriguez-Vicente, AEUniv Salamanca, Canc Res Ctr IBMCC, CSIC, Salamanca, Spain.;Inst Invest Biomed IBSAL, Salamanca, Spain.;Univ Hosp Salamanca, Dept Hematol, Salamanca, Spain. (author)
  • Benito, RUniv Salamanca, Canc Res Ctr IBMCC, CSIC, Salamanca, Spain.;Inst Invest Biomed IBSAL, Salamanca, Spain.;Univ Hosp Salamanca, Dept Hematol, Salamanca, Spain. (author)
  • Mattsson, MattiasUppsala universitet,Cancerprecisionsmedicin(Swepub:uu)matma431 (author)
  • Bonfiglio, SUniv Vita Salute San Raffaele, Milan, Italy.;IRCCS Osped San Raffaele, Milan, Italy. (author)
  • Scarfo, LUniv Vita Salute San Raffaele, Milan, Italy.;IRCCS Osped San Raffaele, Milan, Italy. (author)
  • Mattsson, M (author)
  • Davis, ZUniv Hosp Dorset, Mol Pathol Dept, Bournemouth, Dorset, England. (author)
  • Gogia, AAll India Inst Med Sci AIIMS, New Delhi, India. (author)
  • Rani, LAll India Inst Med Sci AIIMS, New Delhi, India. (author)
  • Baliakas, Panagiotis,1977-Uppsala universitet,Cancerprecisionsmedicin(Swepub:uu)panba345 (author)
  • Foroughi-Asl, HKarolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden. (author)
  • Jylha, CKarolinska Institutet,Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden. (author)
  • Skaftason, AKarolinska Institutet,Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden. (author)
  • Rapado, IHosp Univ 12 Octubre, Madrid, Spain. (author)
  • Miras, FHosp Univ 12 Octubre, Madrid, Spain. (author)
  • Martinez-Lopez, JHosp Univ 12 Octubre, Madrid, Spain.;Spanish Natl Canc Res CNIO, Madrid, Spain. (author)
  • de la Serna, JHosp Univ 12 Octubre, Madrid, Spain.;Spanish Natl Canc Res CNIO, Madrid, Spain. (author)
  • Rivas, JMH (author)
  • Thornton, PBeaumont Hosp, Haematol Dept, Dublin, Ireland. (author)
  • Larrayoz, MJUniv Navarra, Hematol Dis Lab, CIMA LAB Diagnost, Pamplona, Spain.;Navarra Inst Hlth Res, IdiSNA, Pamplona, Spain. (author)
  • Calasanz, MJNavarra Inst Hlth Res, IdiSNA, Pamplona, Spain. (author)
  • Fesus, VSemmelweis Univ, Dept Pathol & Expt Canc Res, HCEMM SE Mol Oncohematol Res Grp, Budapest, Hungary. (author)
  • Matrai, ZCent Hosp Southern Pest, Natl Inst Hematol & Infect Dis, Budapest, Hungary. (author)
  • Bodor, CSemmelweis Univ, Dept Pathol & Expt Canc Res, HCEMM SE Mol Oncohematol Res Grp, Budapest, Hungary. (author)
  • Smedby, KEKarolinska Institutet,Karolinska Inst, Dept Med Solna, Clin Epidemiol Div, Stockholm, Sweden. (author)
  • Espinet, BHosp Mar, Dept Pathol, Mol Cytogenet Lab, Barcelona, Spain.;Hosp Mar Res Inst IMIM, Translat Res Hematol Neoplasms Grp, Barcelona, Spain. (author)
  • Puiggros, AHosp Mar, Dept Pathol, Mol Cytogenet Lab, Barcelona, Spain.;Hosp Mar Res Inst IMIM, Translat Res Hematol Neoplasms Grp, Barcelona, Spain. (author)
  • Gupta, RAll India Inst Med Sci AIIMS, New Delhi, India. (author)
  • Bullinger, LCharite Univ Med Berlin, Dept Hematol Oncol & Canc Immunol, Berlin, Germany.;Free Univ Berlin, Berlin, Germany.;Humboldt Univ, Berlin, Germany. (author)
  • Bosch, FUniv Autonoma Barcelona, Hosp Univ Vall dHebron HUVH, Vall dHebron Inst Oncol VHIO, Dept Hematol,Expt Hematol,Dept Med, Barcelona, Spain. (author)
  • Tazon-Vega, BUniv Autonoma Barcelona, Hosp Univ Vall dHebron HUVH, Vall dHebron Inst Oncol VHIO, Dept Hematol,Expt Hematol,Dept Med, Barcelona, Spain. (author)
  • Baran-Marszak, FHop Avicenne, AP HP, Serv Hematol Biol, Bobigny, France. (author)
  • Oscier, D (author)
  • N'Guyen-Khac, F (author)
  • Zenz, TUniv Hosp, Dept Oncol & Haematol, Zurich, Switzerland.;Univ Zurich, Zurich, Switzerland. (author)
  • Terol, MJUniv Valencia, Dept Hematol, INCL Res Inst, Valencia, Spain. (author)
  • Cuneo, AUniv Ferrara, Dept Med Sci, Hematol, Ferrara, Italy. (author)
  • Hernandez-Sanchez, MUniv Salamanca, Canc Res Ctr IBMCC, CSIC, Salamanca, Spain.;Inst Invest Biomed IBSAL, Salamanca, Spain.;Univ Hosp Salamanca, Dept Hematol, Salamanca, Spain. (author)
  • Pospisilova, SUniv Hosp Brno, Dept Internal Med Hematol & Oncol, Brno, Czech Republic.;Masaryk Univ, Fac Med, Brno, Czech Republic.;Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic. (author)
  • Mills, K (author)
  • Gaidano, GUniv Piemonte Orientale, Dept Translat Med, Div Hematol, Novara, Italy. (author)
  • Niemann, CUCopenhagen Univ Hosp, Rigshosp, Dept Hematol, Copenhagen, Denmark. (author)
  • Campo, EInst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain.;Ctr Invest Biomeed Red Canc CIBERONC, Madrid, Spain.;Hosp Clin Barcelona, Barcelona, Spain.;Univ Barcelona, Barcelona, Spain. (author)
  • Strefford, JCUniv Southampton, Fac Med, Sch Canc Sci, Canc Genom, Southampton, England. (author)
  • Ghia, PUniv Vita Salute San Raffaele, Milan, Italy.;IRCCS Osped San Raffaele, Milan, Italy. (author)
  • Stamatopoulos, KKarolinska Institutet,Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.;Inst Appl Biosci, Ctr Res & Technol Hellas, Thessaloniki, Greece. (author)
  • Rosenquist, RKarolinska Institutet,Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.;Karolinska Univ Hosp, Clin Genet, Solna, Sweden. (author)
  • Karolinska InstitutetKarolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden. (creator_code:org_t)

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  • In:Leukemia: Springer Science and Business Media LLC37:2, s. 339-3471476-55510887-6924

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