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

摘要: 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 IDH2-R172) detected: 5 (0.8%) ET, 8 (1.9%) PV, 13 (4.2%) PMF, (1%) 11 (21.6%) MPN (P<0.01). Mutant was documented in the presence or absence JAK2, MPL TET2 mutations, similar mutational frequencies. However, IDH-mutated more likely to be nullizygous JAK2 46/1 haplotype, especially PMF (P=0.04), less display complex karyotype, disease chronic-phase haplotype nullizygosity (P<0.01; hazard ratio (HR) 2.9, 95% confidence interval (CI) 1.7–5.2), but not status (P=0.55; HR 1.3, CI 0.5–3.4), had an adverse effect on survival. This confirmed by multivariable analysis. contrast, both (P=0.04) (P=0.01), mutation predicted worse The current study clarifies disease- stage-specific incidence prognostic relevance provides additional evidence biological distinct haplotypes.