IDH1 and IDH2 mutation studies in 1473 patients with chronic-, fibrotic- or blast-phase essential thrombocythemia, polycythemia vera or myelofibrosis

A. Tefferi, T. L. Lasho, O. Abdel-Wahab, P. Guglielmelli, J. Patel, D. Caramazza, L. Pieri, C. M. Finke, O. Kilpivaara, M. Wadleigh, M. Mai, R. F. McClure, D. G. Gilliland, R. L. Levine, A. Pardanani, A. M. Vannucchi

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219 Scopus citations

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 (P0.01). 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 (P0.04), and less likely to display complex karyotype, in blast-phase disease (P0.01). In chronic-phase PMF, JAK2 46/1 haplotype nullizygosity (P0.01; hazard ratio (HR) 2.9, 95% confidence interval (CI) 1.7-5.2), but not IDH mutational status (P0.55; 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 (P0.04) and blast-phase MPN (P0.01), 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.

Original languageEnglish (US)
Pages (from-to)1302-1309
Number of pages8
JournalLeukemia
Volume24
Issue number7
DOIs
StatePublished - Jul 2010

Keywords

  • JAK2
  • MPL
  • TET2
  • myeloproliferative

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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    Tefferi, A., Lasho, T. L., Abdel-Wahab, O., Guglielmelli, P., Patel, J., Caramazza, D., Pieri, L., Finke, C. M., Kilpivaara, O., Wadleigh, M., Mai, M., McClure, R. F., Gilliland, D. G., Levine, R. L., Pardanani, A., & Vannucchi, A. M. (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. https://doi.org/10.1038/leu.2010.113