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Mutations of IDH1 and IDH2 genes in early and accelerated phases of myelodysplastic syndromes and MDS/myeloproliferative neoplasms

Leukemia volume 24, pages 1094–1096 (2010)Cite this article

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Acquired somatic mutations affecting the R132 residue of isocitrate dehydrogenase 1 (IDH1) and the R172 residue of IDH2 have been initially described in gliomas, mainly in oligoastrocytic tumors.1 More recently, mutation of the IDH1 gene has been reported in de novo acute myeloid leukemia (AML).2 The prevalence of IDH1 mutations in de novo AML ranges between 5–9% of cases. They are strongly associated with the normal karyotype and are more frequent in patients with NPM1 mutation. IDH1 mutations have no impact on event-free survival in AML patients, except that they have an unfavorable effect on event-free survival in those with intermediate-risk karyotype.3, 4 The fourth exon of both IDH1 and IDH2 genes encodes three arginine residues (R100, R109 and R132 in IDH1 and R140, R149 and R172 in IDH2) that are important for the activity of the proteins.5

Here we have analyzed the sequence of the fourth exon of IDH1 and IDH2 genes established from the bone marrow DNA of 100 cases of myelodysplastic syndrome (MDS) including all subtypes of the WHO 2008 classification, 90 cases of MDS/myeloproliferative neoplasm (MPN), including 88 cases of chronic myelomonocytic leukemia and 2 cases of refractory anemia with ringed sideroblast and thrombocytosis, and 41 cases of AML post-MDS and AML post-MDS/MPN, referred to as secondary AML (sAML). To identify associations between molecular events, we also established the TET2 and JAK2 status of the samples.

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Acknowledgements

We thank Professor D Bouscary, Dr J Tamburini and Dr S Park for including the patients. This work was supported by INSERM, INCa and the DRRC (Direction régionale de la Recherche Clinique AP-HP).

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Authors and Affiliations

  1. Assistance Publique-Hôpitaux de Paris (AP-HP), Service d’Hématologie Biologique, Hôpital Cochin-Hôtel-Dieu, Paris, France

    O Kosmider, L Slama, C Lacombe, O A Bernard & M Fontenay

  2. Département d′Immuno-Hématologie, Institut Cochin, Paris, France

    O Kosmider, L Slama, F Dreyfus, C Lacombe & M Fontenay

  3. Inserm U1016, CNRS UMR 8104—Université Paris Descartes, Paris, France

    O Kosmider, L Slama, F Dreyfus, C Lacombe & M Fontenay

  4. Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR) 8104, Paris, France

    O Kosmider, L Slama, F Dreyfus, C Lacombe & M Fontenay

  5. Faculté de Médecine René Descartes, Université Paris Descartes, Paris, France

    O Kosmider, F Dreyfus, C Lacombe & M Fontenay

  6. Laboratoire d’Oncologie Moléculaire, Centre de Recherche en Cancérologie, Inserm UMR891, Institut Paoli-Calmettes, Marseille, France

    V Gelsi-Boyer & D Birnbaum

  7. Département de Médecine Interne, AP-HP, Unité Fonctionnelle d’Hématologie, Hôpital Cochin, Paris, France

    F Dreyfus

  8. Service de Médecine Interne, CHU Purpan, Toulouse, France

    O Beyne-Rauzy

  9. Service des Maladies du Sang, Hôpital Huriez Centre de Recherche Inserm 837, Institut pour la Recherche sur le Cancer de Lille (IRCL), Lille, France

    B Quesnel

  10. Service des Maladies du Sang, CHU, Angers, France

    M Hunault-Berger

  11. Service de Médecine, CHR Avignon, Avignon, France

    B Slama

  12. Service d’Hématologie, Institut Paoli Calmettes, Marseille, France

    N Vey

  13. Inserm U1009, Institut Gustave Roussy, Université Paris XI, Villejuif, France

    E Solary

  14. Inserm U985, Université Paris Descartes, Paris, France

    O A Bernard

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  1. O Kosmider
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  2. V Gelsi-Boyer
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  5. O Beyne-Rauzy
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  7. M Hunault-Berger
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  8. B Slama
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  9. N Vey
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  12. D Birnbaum
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  13. O A Bernard
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  14. M Fontenay
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Corresponding author

Correspondence to M Fontenay.

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Kosmider, O., Gelsi-Boyer, V., Slama, L. et al. Mutations of IDH1 and IDH2 genes in early and accelerated phases of myelodysplastic syndromes and MDS/myeloproliferative neoplasms. Leukemia 24, 1094–1096 (2010). https://doi.org/10.1038/leu.2010.52

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