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

被引：266

作者：

Tefferi, A. ^{[1
]}

Lasho, T. L. ^{[1
]}

Abdel-Wahab, O. ^{[2
,3
]}

Guglielmelli, P. ^{[4
]}

Patel, J. ^{[2
,3
]}

Caramazza, D. ^{[5
]}

Pieri, L. ^{[4
]}

Finke, C. M. ^{[1
]}

Kilpivaara, O. ^{[2
,3
]}

Wadleigh, M. ^{[6
]}

Mai, M. ^{[7
]}

McClure, R. F. ^{[7
]}

Gilliland, D. G. ^{[6
]}

Levine, R. L. ^{[2
,3
]}

Pardanani, A. ^{[1
]}

Vannucchi, A. M. ^{[4
]}

机构：

[1] Mayo Clin, Div Hematol, Dept Med, Rochester, MN 55905 USA

[2] Mem Sloan Kettering Canc Ctr, Dept Med, Human Oncol & Pathogenesis Program, New York, NY 10021 USA

[3] Mem Sloan Kettering Canc Ctr, Dept Med, Leukemia Serv, New York, NY 10021 USA

[4] Univ Florence, UF Ematol, Dipartimento Area Crit Med Chirurg, Azienda Osped Univ Careggi,Ist Toscano Tumori, Florence, Italy

[5] Policlin Univ Palermo, Cattedra & UO Ematol, Palermo, Italy

[6] Harvard Univ, Brigham & Womens Hosp, Div Hematol,Dept Med, Dana Farber Canc Inst,Sch Med, Boston, MA 02115 USA

[7] Mayo Clin, Div Hematopathol, Dept Lab Med, Rochester, MN USA

来源：

LEUKEMIA | 2010年 / 24卷 / 07期

关键词：

JAK2; MPL; TET2; myeloproliferative; JAK2; 46/1; HAPLOTYPE; INTERNATIONAL WORKING GROUP; ISOCITRATE-DEHYDROGENASE; PROGNOSTIC SCORING SYSTEM; MYELOPROLIFERATIVE NEOPLASMS; CONFERS SUSCEPTIBILITY; ACTIVATING MUTATION; MYELOID METAPLASIA; TET2; MUTATIONS; LEUKEMIA;

D O I：

10.1038/leu.2010.113

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

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 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

引用

页码：1302 / 1309

页数：8

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