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

   

Authors:	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.
Article Title:	IDH1 and IDH2 mutation studies in 1473 patients with chronic-, fibrotic- or blast-phase essential thrombocythemia, polycythemia vera or myelofibrosis
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. © 2010 Macmillan Publishers Limited All rights reserved.
Keywords:	survival; adolescent; adult; aged; aged, 80 and over; middle aged; myelofibrosis; young adult; unclassified drug; gene mutation; major clinical study; mutation; janus kinase 2; primary myelofibrosis; polymerase chain reaction; cohort studies; haplotype; mutation rate; karyotype; polycythemia vera; thrombocythemia; isocitrate dehydrogenase; thrombocythemia, essential; myeloproliferative; isocitrate dehydrogenase 1; isocitrate dehydrogenase isoenzyme; receptors, thrombopoietin; jak2; mpl; tet2; blast crisis
Journal Title:	Leukemia
Volume:	24
Issue:	7
ISSN:	0887-6924
Publisher:	Nature Publishing Group
Date Published:	2010-07-01
Start Page:	1302
End Page:	1309
Language:	English
DOI:	10.1038/leu.2010.113
PUBMED:	20508616
PROVIDER:	scopus
PMCID:	PMC3035975
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-77954658823&partnerID=40&md5=7b4774dd93ea2a3d489c9141be597122
Notes:	--- - "Cited By (since 1996): 17" - "Export Date: 20 April 2011" - "CODEN: LEUKE" - "Source: Scopus"

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