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

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dc.contributor.author Tefferi, A
dc.contributor.author Lasho, T L
dc.contributor.author Abdel-Wahab, O
dc.contributor.author Guglielmelli, P
dc.contributor.author Caramazza, D
dc.contributor.author Pieri, L
dc.contributor.author Finke, C M
dc.contributor.author Kilpivaara, O
dc.contributor.author Mai, M
dc.contributor.author Gilliland, Dwight
dc.contributor.author Pardanani, A
dc.contributor.author Vannucchi, A M
dc.contributor.author Patel, J.
dc.contributor.author Wadleigh, Martha
dc.contributor.author McClure, R. F.
dc.contributor.author Levine, Robert A.
dc.date.accessioned 2011-09-21T14:51:19Z
dc.date.issued 2010
dc.identifier.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. en_US
dc.identifier.issn 0887-6924 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:5136364
dc.description.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. en_US
dc.language.iso en_US en_US
dc.publisher Nature Publishing Group en_US
dc.relation.isversionof doi:10.1038/leu.2010.113 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3035975/pdf/ en_US
dash.license LAA
dc.subject JAK2 en_US
dc.subject MPL en_US
dc.subject TET2 en_US
dc.subject myeloproliferative en_US
dc.title IDH1 and IDH2 Mutation Studies in 1473 Patients with Chronic-, Fibrotic- or Blast-Phase Essential Thrombocythemia, Polycythemia Vera or Myelofibrosis en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal Leukemia en_US
dash.depositing.author Wadleigh, Martha
dc.date.available 2011-09-21T14:51:19Z
dash.affiliation.other HMS^Medicine-Brigham and Women's Hospital en_US
dash.affiliation.other HMS^Medicine-Brigham and Women's Hospital en_US

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