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

Ayalew Tefferi, T. L. Lasho, O. Abdel-Wahab, P. Guglielmelli, J. Patel, D. Caramazza, L. Pieri, C. M. Finke, O. Kilpivaara, M. Wadleigh, M. Mai, R. F. McClure, D. G. Gilliland, R. L. Levine, Animesh D Pardanani, A. M. Vannucchi

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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.

Original languageEnglish (US)
Pages (from-to)1302-1309
Number of pages8
JournalLeukemia
Volume24
Issue number7
DOIs
StatePublished - Jul 2010

Fingerprint

Blast Crisis
Essential Thrombocythemia
Isocitrate Dehydrogenase
Polycythemia Vera
Primary Myelofibrosis
Mutation
Haplotypes
Neoplasms
Confidence Intervals
Survival
Karyotype
Incidence

Keywords

  • JAK2
  • MPL
  • myeloproliferative
  • TET2

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine
  • Medicine(all)

Cite this

IDH1 and IDH2 mutation studies in 1473 patients with chronic-, fibrotic- or blast-phase essential thrombocythemia, polycythemia vera or myelofibrosis. / Tefferi, Ayalew; 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, Animesh D; Vannucchi, A. M.

In: Leukemia, Vol. 24, No. 7, 07.2010, p. 1302-1309.

Research output: Contribution to journalArticle

Tefferi, A, Lasho, TL, Abdel-Wahab, O, Guglielmelli, P, Patel, J, Caramazza, D, Pieri, L, Finke, CM, Kilpivaara, O, Wadleigh, M, Mai, M, McClure, RF, Gilliland, DG, Levine, RL, Pardanani, AD & Vannucchi, AM 2010, 'IDH1 and IDH2 mutation studies in 1473 patients with chronic-, fibrotic- or blast-phase essential thrombocythemia, polycythemia vera or myelofibrosis', Leukemia, vol. 24, no. 7, pp. 1302-1309. https://doi.org/10.1038/leu.2010.113
Tefferi, Ayalew ; 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, Animesh D ; Vannucchi, A. M. / IDH1 and IDH2 mutation studies in 1473 patients with chronic-, fibrotic- or blast-phase essential thrombocythemia, polycythemia vera or myelofibrosis. In: Leukemia. 2010 ; Vol. 24, No. 7. pp. 1302-1309.
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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.",
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AU - Guglielmelli, P.

AU - Patel, J.

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AU - Pieri, L.

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AU - Mai, M.

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