Back to Search
Start Over
Impact of genotype on leukaemic transformation in polycythaemia vera and essential thrombocythaemia.
- Source :
-
British journal of haematology [Br J Haematol] 2017 Sep; Vol. 178 (5), pp. 764-771. Date of Electronic Publication: 2017 May 23. - Publication Year :
- 2017
-
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.<br /> (© 2017 John Wiley & Sons Ltd.)
- Subjects :
- Adolescent
Adult
Aged
Aged, 80 and over
Calreticulin genetics
Child
Female
Follow-Up Studies
Genotype
Humans
Janus Kinase 2 genetics
Kaplan-Meier Estimate
Leukemia, Myeloid mortality
Male
Middle Aged
Mutation
Myelodysplastic Syndromes mortality
Polycythemia Vera mortality
Prognosis
Risk Factors
Spain epidemiology
Thrombocythemia, Essential mortality
Young Adult
Cell Transformation, Neoplastic genetics
Leukemia, Myeloid genetics
Myelodysplastic Syndromes genetics
Polycythemia Vera genetics
Thrombocythemia, Essential genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1365-2141
- Volume :
- 178
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- British journal of haematology
- Publication Type :
- Academic Journal
- Accession number :
- 28542718
- Full Text :
- https://doi.org/10.1111/bjh.14762