Impact of genotype on leukaemic transformation in polycythaemia vera and essential thrombocythaemia.
Br J Haematol
; 178(5): 764-771, 2017 09.
Article
em En
| MEDLINE
| ID: mdl-28542718
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.
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Base de dados:
MEDLINE
Assunto principal:
Policitemia Vera
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Síndromes Mielodisplásicas
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Leucemia Mieloide
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Transformação Celular Neoplásica
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Trombocitemia Essencial
Tipo de estudo:
Clinical_trials
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Etiology_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adolescent
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Adult
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Aged
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Aged80
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Child
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Female
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Humans
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Male
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Middle aged
País como assunto:
Europa
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article