Title:
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Impact of genotype on leukaemic transformation in polycythaemia vera and essential thrombocythaemia
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Author:
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Alvarez-Larrán, Alberto; Senín Magan, Maria Alicia; Fernández Rodríguez, M. Concepción; Pereira, Arturo; Arellano-Rodrigo, Arturo; Gómez, Montse; Ferrer-Marín, Francisca; Martínez-López, Joaquín; Camacho Díaz, Laura; Colomer, Dolors; Angona Figueras, Anna; Navarro, Blanca; Cervantes, Francisco; Besses Raebel, Carles; Bellosillo Paricio, Beatriz; Hernández-Boluda, Juan Carlos
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Abstract:
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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 |
Subject(s):
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-Leucèmia -Essential thrombocythaemia -Genotype -Myeloid leukaemia -Polycythaemia vera -Prognostic factors |
Rights:
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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. |
Document type:
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Article Article - Accepted version |
Published by:
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Wiley
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