Impact of genotype on leukaemic transformation in polycythaemia vera and essential thrombocythaemia

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  • dc.contributor.author Alvarez-Larrán, Albertoca
  • dc.contributor.author Senín Magan, Maria Aliciaca
  • dc.contributor.author Fernández Rodríguez, M. Concepciónca
  • dc.contributor.author Pereira, Arturoca
  • dc.contributor.author Arellano-Rodrigo, Arturoca
  • dc.contributor.author Gómez, Montseca
  • dc.contributor.author Ferrer-Marín, Franciscaca
  • dc.contributor.author Martínez-López, Joaquínca
  • dc.contributor.author Camacho Díaz, Lauraca
  • dc.contributor.author Colomer Pujol, Dolorsca
  • dc.contributor.author Angona Figueras, Annaca
  • dc.contributor.author Navarro, Blancaca
  • dc.contributor.author Cervantes, Franciscoca
  • dc.contributor.author Besses Raebel, Carlesca
  • dc.contributor.author Bellosillo Paricio, Beatrizca
  • dc.contributor.author Hernández-Boluda, Juan Carlosca
  • dc.date.accessioned 2018-04-24T07:29:09Z
  • dc.date.issued 2017
  • dc.description.abstract The influence of driver mutations on leukaemic transformation was analysed in 1747 patients with polycythaemia vera or essential thrombocythaemia. With a median follow-up of 7·2 years, 349 patients died and 62 progressed to acute leukaemia or myelodysplastic syndrome. Taking death as a competing risk, CALR genotype was associated with a lower risk of transformation [subdistribution hazard ratio (SHR): 0·13, 95% confidence interval (CI): 0·2-0·9, P = 0·039], whereas JAK2 V617F showed borderline significance for higher risk (SHR: 2·05, 95% CI: 0·9-4·6, P = 0·09). Myelofibrotic transformation increased leukaemic risk, except in CALR-mutated patients. Next generation sequencing of 51 genes at the time of transformation showed additional mutations (median number: 3; range: 1-5) in 25 out of 29 (86%) assessable cases. Mutations (median: 1; range: 1-3) were detected in 67% of paired samples from the chronic phase. Leukaemia appeared in a JAK2 V617F negative clone in 17 (58%) cases, eleven of them being previously JAK2 V617F-positive. JAK2 V617F-mutated leukaemia was significantly associated with complex karyotype and acquisition of TP53 mutations, whereas EZH2 and RUNX1 mutations were more frequent in JAK2 V617F-negative leukaemia. Survival was longer in JAK2 V617F-unmutated leukaemia (343 days vs. 95 days, P = 0·003). In conclusion, CALR genotype is associated with a lower risk of leukaemic transformation. Leukaemia arising in a JAK2 V617F-negative clone is TP53 independent and shows better survival
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Alvarez-Larrán A, Senín A, Fernández-Rodríguez C, Pereira A, Arellano-Rodrigo E, Gómez M.et al. Impact of genotype on leukaemic transformation in polycythaemia vera and essential thrombocythaemia. Br J Haematol. 2017 Sep;178(5):764-71. DOI: 10.1111/bjh.14762
  • dc.identifier.doi http://dx.doi.org/10.1111/bjh.14762
  • dc.identifier.issn 0007-1048
  • dc.identifier.uri http://hdl.handle.net/10230/34428
  • dc.language.iso eng
  • dc.publisher Wileyca
  • dc.relation.ispartof British Journal of Haematology. 2017 Sep;178(5):764-71
  • dc.rights This is the peer reviewed version of the following article: Alvarez-Larrán A, Senín A, Fernández-Rodríguez C, Pereira A, Arellano-Rodrigo E, Gómez M.et al. Impact of genotype on leukaemic transformation in polycythaemia vera and essential thrombocythaemia. Br J Haematol. 2017 Sep;178(5):764-771, which has been published in final form at http://dx.doi.org/10.1111/bjh.14762. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.subject.keyword Essential thrombocythaemia
  • dc.subject.keyword Genotype
  • dc.subject.keyword Myeloid leukaemia
  • dc.subject.keyword Polycythaemia vera
  • dc.subject.keyword Prognostic factors
  • dc.subject.other Leucèmia
  • dc.title Impact of genotype on leukaemic transformation in polycythaemia vera and essential thrombocythaemiaca
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/acceptedVersion

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