IDH1 and IDH2 Mutation Studies in 1473 Patients with Chronic-, Fibrotic- or Blast-Phase Essential Thrombocythemia, Polycythemia Vera or Myelofibrosis
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IDH1 and IDH2 Mutation Studies in 1473 Patients with Chronic-, Fibrotic- or Blast-Phase Essential Thrombocythemia, Polycythemia Vera or Myelofibrosis
| Title: | IDH1 and IDH2 Mutation Studies in 1473 Patients with Chronic-, Fibrotic- or Blast-Phase Essential Thrombocythemia, Polycythemia Vera or Myelofibrosis |
| Author: |
Tefferi, A; Lasho, T L; Abdel-Wahab, O; Guglielmelli, P; Caramazza, D; Pieri, L; Finke, C M; Kilpivaara, O; Mai, M; Gilliland, Dwight; Pardanani, A; Vannucchi, A M; Patel, J.; Wadleigh, Martha; McClure, R. F.; Levine, Robert A.
Note: Order does not necessarily reflect citation order of authors. |
| Citation: | Tefferi, A., T. L. Lasho, O. Abdel-Wahab, P. Guglielmelli, J. Patel, D. Caramazza, L. Pieri, et al. 2010. IDH1 and IDH2 mutation studies in 1473 patients with chronic-, fibrotic- or blast-phase essential thrombocythemia, polycythemia vera or myelofibrosis. Leukemia 24(7): 1302-1309. |
| Full Text & Related Files: |
3035975.pdf (471.3Kb; PDF) 
|
| Abstract: | In a multi-institutional collaborative project, 1473 patients with myeloproliferative neoplasms (MPN) were screened for isocitrate dehydrogenase 1 (IDH1)/IDH2 mutations: 594 essential thrombocythemia (ET), 421 polycythemia vera (PV), 312 primary myelofibrosis (PMF), 95 post-PV/ET MF and 51 blast-phase MPN. A total of 38 IDH mutations (18 IDH1-R132, 19 IDH2-R140 and 1 IDH2-R172) were detected: 5 (0.8%) ET, 8 (1.9%) PV, 13 (4.2%) PMF, 1 (1%) post-PV/ET MF and 11 (21.6%) blast-phase MPN (P<0.01). Mutant IDH was documented in the presence or absence of JAK2, MPL and TET2 mutations, with similar mutational frequencies. However, IDH-mutated patients were more likely to be nullizygous for JAK2 46/1 haplotype, especially in PMF (P=0.04), and less likely to display complex karyotype, in blast-phase disease (P<0.01). In chronic-phase PMF, JAK2 46/1 haplotype nullizygosity (P<0.01; hazard ratio (HR) 2.9, 95% confidence interval (CI) 1.7–5.2), but not IDH mutational status (P=0.55; HR 1.3, 95% CI 0.5–3.4), had an adverse effect on survival. This was confirmed by multivariable analysis. In contrast, in both blast-phase PMF (P=0.04) and blast-phase MPN (P=0.01), the presence of an IDH mutation predicted worse survival. The current study clarifies disease- and stage-specific IDH mutation incidence and prognostic relevance in MPN and provides additional evidence for the biological effect of distinct JAK2 haplotypes. |
| Published Version: | doi:10.1038/leu.2010.113 |
| Other Sources: | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3035975/pdf/ |
| Terms of Use: | This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA |
| Citable link to this page: | http://nrs.harvard.edu/urn-3:HUL.InstRepos:5136364 |
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