Show simple item record

dc.contributor.authorDiop, Fary
dc.contributor.authorMoia, Riccardo
dc.contributor.authorFavini, Chiara
dc.contributor.authorSpaccarotella, Elisa
dc.contributor.authorDe Paoli, Lorenzo
dc.contributor.authorBruscaggin, Alessio
dc.contributor.authorSpina, Valeria
dc.contributor.authorTerzi-di-Bergamo, Lodovico
dc.contributor.authorArruga, Francesca
dc.contributor.authorTarantelli, Chiara
dc.contributor.authorDeambrogi, Clara
dc.contributor.authorRasi, Silvia
dc.contributor.authorAdhinaveni, Ramesh
dc.contributor.authorPatriarca, Andrea
dc.contributor.authorFavini, Simone
dc.contributor.authorSagiraju, Sruthi
dc.contributor.authorJabangwe, Clive
dc.contributor.authorKodipad, Ahad A
dc.contributor.authorPeroni, Denise
dc.contributor.authorMauro, Francesca R
dc.contributor.authorGiudice, Ilaria Del
dc.contributor.authorForconi, Francesco
dc.contributor.authorCortelezzi, Agostino
dc.contributor.authorZaja, Francesco
dc.contributor.authorBomben, Riccardo
dc.contributor.authorRossi, Francesca Maria
dc.contributor.authorVisco, Carlo
dc.contributor.authorChiarenza, Annalisa
dc.contributor.authorRigolin, Gian Matteo
dc.contributor.authorMarasca, Roberto
dc.contributor.authorCoscia, Marta
dc.contributor.authorPerbellini, Omar
dc.contributor.authorTedeschi, Alessandra
dc.contributor.authorLaurenti, Luca
dc.contributor.authorMotta, Marina
dc.contributor.authorDonaldson, David
dc.contributor.authorWeir, Phil
dc.contributor.authorMills, Ken
dc.contributor.authorThornton, Patrick
dc.contributor.authorLawless, Sarah
dc.contributor.authorBertoni, Francesco
dc.contributor.authorPoeta, Giovanni Del
dc.contributor.authorCuneo, Antonio
dc.contributor.authorFollenzi, Antonia
dc.contributor.authorGattei, Valter
dc.contributor.authorBoldorini, Renzo Luciano
dc.contributor.authorCatherwood, Mark
dc.contributor.authorDeaglio, Silvia
dc.contributor.authorFoà, Robin
dc.contributor.authorGaidano, Gianluca
dc.contributor.authorRossi, Davide
dc.date.accessioned2021-08-11T14:53:15Z
dc.date.available2021-08-11T14:53:15Z
dc.date.issued2020-01-31
dc.identifier.pmid31371416
dc.identifier.doi10.3324/haematol.2019.219550
dc.identifier.urihttp://hdl.handle.net/10147/630029
dc.description.abstractBIRC3 is a recurrently mutated gene in chronic lymphocytic leukemia (CLL) but the functional implications of BIRC3 mutations are largely unexplored. Furthermore, little is known about the prognostic impact of BIRC3 mutations in CLL cohorts homogeneously treated with first-line fludarabine, cyclophosphamide, and rituximab (FCR). By immunoblotting analysis, we showed that the non-canonical nuclear factor-κB pathway is active in BIRC3-mutated cell lines and in primary CLL samples, as documented by the stabilization of MAP3K14 and by the nuclear localization of p52. In addition, BIRC3-mutated primary CLL cells are less sensitive to flu-darabine. In order to confirm in patients that BIRC3 mutations confer resistance to fludarabine-based chemoimmunotherapy, a retrospective multicenter cohort of 287 untreated patients receiving first-line FCR was analyzed by targeted next-generation sequencing of 24 recurrently mutated genes in CLL. By univariate analysis adjusted for multiple comparisons BIRC3 mutations identify a poor prognostic subgroup of patients in whom FCR treatment fails (median progression-free survival: 2.2 years, P<0.001) similar to cases harboring TP53 mutations (median progression-free survival: 2.6 years, P<0.0001). BIRC3 mutations maintained an independent association with an increased risk of progression with a hazard ratio of 2.8 (95% confidence interval 1.4-5.6, P=0.004) in multivariate analysis adjusted for TP53 mutation, 17p deletion and IGHV mutation status. If validated, BIRC3 mutations may be used as a new molecular predictor to select high-risk patients for novel frontline therapeutic approaches.en_US
dc.languageen
dc.language.isoenen_US
dc.rightsCopyright© 2020 Ferrata Storti Foundation.
dc.subjectLEUKAEMIAen_US
dc.subjectGENETIC FACTORSen_US
dc.titleBiological and clinical implications of mutations in chronic lymphocytic leukemia.en_US
dc.typeArticleen_US
dc.typeOtheren_US
dc.identifier.eissn1592-8721
dc.identifier.journalHaematologicaen_US
dc.description.peer-reviewpeer-reviewen_US
dc.source.journaltitleHaematologica
dc.source.volume105
dc.source.issue2
dc.source.beginpage448
dc.source.endpage456
refterms.dateFOA2021-08-11T14:53:16Z
dc.source.countryItaly


Files in this item

Thumbnail
Name:
9529-Article Text-70677-1-10-2 ...
Size:
2.836Mb
Format:
PDF

This item appears in the following Collection(s)

Show simple item record