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Genomic analysis of primary and secondary myelofibrosis redefines the prognostic impact of ASXL1 mutations: a FIM study.

dc.rights.licenseauthentificationen_US
dc.contributor.authorLUQUE PAZ, Damien
dc.contributor.authorRIOU, Jeremie
dc.contributor.authorVERGER, Emmanuelle
dc.contributor.authorCASSINAT, Bruno
dc.contributor.authorCHAUVEAU, Aurelie
dc.contributor.authorIANOTTO, Jean-Christophe
dc.contributor.authorDUPRIEZ, Brigitte
dc.contributor.authorBOYER, Françoise
dc.contributor.authorRENARD, Maxime
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorMANSIER, Olivier
dc.contributor.authorMURATI, Anne
dc.contributor.authorREY, Jerome
dc.contributor.authorETIENNE, Gabriel
dc.contributor.authorMANSAT-DE MAS, Veronique
dc.contributor.authorTAVITIAN, Suzanne
dc.contributor.authorNIBOUREL, Olivier
dc.contributor.authorGIRAULT, Stephane
dc.contributor.authorLE BRIS, Yannick
dc.contributor.authorGIRODON, François
dc.contributor.authorRANTA, Dana
dc.contributor.authorCHOMEL, Jean-Claude
dc.contributor.authorCONY-MAKHOUL, Pascale
dc.contributor.authorSUJOBERT, Pierre
dc.contributor.authorROBLES, Margot
dc.contributor.authorBEN ABDELALI, Raouf
dc.contributor.authorKOSMIDER, Olivier
dc.contributor.authorCOTTIN, Laurane
dc.contributor.authorROY, Lydia
dc.contributor.authorSLOMA, Ivan
dc.contributor.authorVACHERET, Fabienne
dc.contributor.authorWEMEAU, Mathieu
dc.contributor.authorMOSSUZ, Pascal
dc.contributor.authorSLAMA, Borhane
dc.contributor.authorCUSSAC, Vincent
dc.contributor.authorDENIS, Guillaume
dc.contributor.authorWALTER-PETRICH, Anouk
dc.contributor.authorBURRONI, Barbara
dc.contributor.authorJEZEQUEL, Nathalie
dc.contributor.authorGIRAUDIER, Stephane
dc.contributor.authorLIPPERT, Eric
dc.contributor.authorSOCIE, Gerard
dc.contributor.authorKILADJIAN, Jean-Jacques
dc.contributor.authorUGO, Valérie
hal.structure.identifierUniversité d'Angers [UA]
hal.structure.identifierGénétique, génomique fonctionnelle et biotechnologies (UMR 1078) [GGB]
hal.structure.identifierInnate Immunity and Immunotherapy [CRCINA-ÉQUIPE 7]
dc.contributor.authorUGO, Valerie
dc.date.accessioned2021-06-10T08:07:43Z
dc.date.available2021-06-10T08:07:43Z
dc.date.issued2021-03-09
dc.identifier.issn2473-9537en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/79064
dc.description.abstractEnWe aimed to study the prognostic impact of the mutational landscape in primary and secondary myelofibrosis. The study included 479 patients with myelofibrosis recruited from 24 French Intergroup of Myeloproliferative Neoplasms (FIM) centers. The molecular landscape was studied by high-throughput sequencing of 77 genes. A Bayesian network allowed the identification of genomic groups whose prognostic impact was studied in a multistate model considering transitions from the 3 conditions: myelofibrosis, acute leukemia, and death. Results were validated using an independent, previously published cohort (n = 276). Four genomic groups were identified: patients with TP53 mutation; patients with ≥1 mutation in EZH2, CBL, U2AF1, SRSF2, IDH1, IDH2, NRAS, or KRAS (high-risk group); patients with ASXL1-only mutation (ie, no associated mutation in TP53 or high-risk genes); and other patients. A multistate model found that both TP53 and high-risk groups were associated with leukemic transformation (hazard ratios [HRs] [95% confidence interval], 8.68 [3.32-22.73] and 3.24 [1.58-6.64], respectively) and death from myelofibrosis (HRs, 3.03 [1.66-5.56] and 1.77 [1.18-2.67], respectively). ASXL1-only mutations had no prognostic value that was confirmed in the validation cohort. However, ASXL1 mutations conferred a worse prognosis when associated with a mutation in TP53 or high-risk genes. This study provides a new definition of adverse mutations in myelofibrosis with the addition of TP53, CBL, NRAS, KRAS, and U2AF1 to previously described genes. Furthermore, our results argue that ASXL1 mutations alone cannot be considered detrimental.
dc.language.isoENen_US
dc.subject.enClinical Trials and Observations
dc.subject.enMyeloid Neoplasia
dc.title.enGenomic analysis of primary and secondary myelofibrosis redefines the prognostic impact of ASXL1 mutations: a FIM study.
dc.title.alternativeBlood Adven_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1182/bloodadvances.2020003444en_US
dc.subject.halSciences du Vivant [q-bio]/Canceren_US
dc.identifier.pubmed33666653en_US
bordeaux.journalBlood Advancesen_US
bordeaux.page1442-1451en_US
bordeaux.volume5en_US
bordeaux.hal.laboratoriesBiologie des maladies cardiovasculaires - U1034en_US
bordeaux.issue5en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.import.sourcepubmed
hal.exportfalse
workflow.import.sourcepubmed
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