TY - JOUR
T1 - IDH1 and IDH2 mutation studies in 1473 patients with chronic-, fibrotic- or blast-phase essential thrombocythemia, polycythemia vera or myelofibrosis
AU - Tefferi, A.
AU - Lasho, T. L.
AU - Abdel-Wahab, O.
AU - Guglielmelli, P.
AU - Patel, J.
AU - Caramazza, D.
AU - Pieri, L.
AU - Finke, C. M.
AU - Kilpivaara, O.
AU - Wadleigh, M.
AU - Mai, M.
AU - McClure, R. F.
AU - Gilliland, D. G.
AU - Levine, R. L.
AU - Pardanani, A.
AU - Vannucchi, A. M.
N1 - Funding Information:
This study is supported in part by grants from the ‘Myeloproliferative Disorders Foundation, Chicago, IL, USA’, ‘The Henry J. Predolin Foundation for Research in Leukemia, Mayo Clinic, Rochester, MN, USA’ and ‘Associazione Italiana per la Ricerca sul Cancro-AIRC Milan, Italy, to AMV’.
PY - 2010/7
Y1 - 2010/7
N2 - 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.
AB - 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.
KW - JAK2
KW - MPL
KW - TET2
KW - myeloproliferative
UR - http://www.scopus.com/inward/record.url?scp=77954658823&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77954658823&partnerID=8YFLogxK
U2 - 10.1038/leu.2010.113
DO - 10.1038/leu.2010.113
M3 - Article
C2 - 20508616
AN - SCOPUS:77954658823
SN - 0887-6924
VL - 24
SP - 1302
EP - 1309
JO - Leukemia
JF - Leukemia
IS - 7
ER -