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Low prevalence of IDH1 gene mutation in childhood AML in Italy

Leukemia volume 25, pages 173–174 (2011)Cite this article

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Acute myeloid leukemia (AML) is an heterogeneous disease, with still a dismal prognosis, which requires bone marrow transplantation (BMT) as a most effective treatment in the majority of patients.1 The recent and continuously increasing identification of genetic mutations allows to define prognostic subgroups and potential targets for new treatments, aiming to improve the survival rates. The first attempt to perform the whole-genome sequencing of an adult AML case identified, in addition to known aberrancies, the mutation of the IDH1 gene as a novel acquired somatic mutation in AML,2 which could represent a new genetic entity in both pediatric and adult AML.

The IDH1 gene encodes for NADP+-dependent isocitrate dehydrogenase 1, an enzyme that catalyzes the oxidative decarboxylation of isocitrate to α-ketoglutarate. Acquired somatic mutations of the R132 residue of IDH1 have previously been described in gliomas,3 and then detected in adults with de novo AML, with a prevalence of 4.4%, rising to 16% in those with a normal karyotype.2, 4, 5 Although the role of IDH1 mutations in the pathogenesis of AML is still unclear, it has been suggested that an alteration in IDH1 expression may lead to a depletion of cellular α-ketoglutarate, activating the downstream oncogenic HIF-1α pathway.

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Acknowledgements

This work was supported by Comitato ML Verga and Fondazione Tettamanti (Monza), Fondazione Città della Speranza (Padova), Associazione Italiana per la Ricerca sul Cancro (AIRC), Fondazione Cariplo, Ministero dell'Istruzione and Università e Ricerca (MIUR). We thank Vincenzo Rossi, Dr Sabrina Gelain and Dr Alessandra Beghin for their excellent technical support.

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Authors and Affiliations

  1. Dipartimento di Pediatria, Laboratorio di Emato-Oncologia, Università di Padova, Padova, Italy

    M Pigazzi, F Martinolli & G Basso

  2. Centro Ricerca Tettamanti, Clinica Pediatrica Università Milano-Bicocca, Ospedale San Gerardo, Monza, Italy

    G Ferrari, A Biondi & G Cazzaniga

  3. Oncologia ed Ematologia Pediatrica ‘Lalla Seràgnoli’, Università di Bologna, Bologna, Italy

    R Masetti & A Pession

  4. Istituto di Ematologia ed Immunologia Clinica, Università di Perugia, Perugia, Italy

    B Falini

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  1. M Pigazzi
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  2. G Ferrari
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  4. B Falini
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  8. A Pession
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  9. G Cazzaniga
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Correspondence to A Pession.

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Pigazzi, M., Ferrari, G., Masetti, R. et al. Low prevalence of IDH1 gene mutation in childhood AML in Italy. Leukemia 25, 173–174 (2011). https://doi.org/10.1038/leu.2010.229

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