Journal
LEUKEMIA
Volume 24, Issue 7, Pages 1302-1309Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/leu.2010.113
Keywords
JAK2; MPL; TET2; myeloproliferative
Categories
Funding
- Myeloproliferative Disorders Foundation, Chicago, IL, USA
- Henry J. Predolin Foundation for Research in Leukemia, Mayo Clinic, Rochester, MN, USA
- Associazione Italiana per la Ricerca sul Cancro-AIRC Milan, Italy
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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. Leukemia (2010) 24, 1302-1309; doi:10.1038/leu.2010.113; published online 27 May 2010
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