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Acute lymphoblastic leukemia

Age-related clinical and biological features of PTEN abnormalities in T-cell acute lymphoblastic leukaemia

Leukemia volume 31, pages 2594–2600 (2017)Cite this article

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Abstract

The tumour suppressor gene PTEN is commonly altered in T-cell acute lymphoblastic leukaemia but its prognostic impact is still debated. We screened a cohort of 573 fully characterised adult and paediatric T-cell acute lymphoblastic leukaemia (T-ALL) patients for genomic PTEN abnormalities. PTEN-inactivating mutations and/or deletions were identified in 91 cases (16%), including 18% of paediatric (49/277) and 14% of adult cases (42/296). Thirty-four patients harboured only mutations, 12 cases demonstrated only large deletions and 9 only microdeletions. About 36 patients had combined alterations. Different mechanisms of PTEN inactivation predicted differences in the clinical outcome for both adult and paediatric patients treated according to the GRAALL03/05 and FRALLE2000 protocols. Whereas large deletions predicted lower 5-year overall survival (P=0.0053 in adults, P=0.001 in children) and disease-free survival (P=0.0009 in adults, P=0.0002 in children), mutations were not associated with a worse prognosis. The prognostic impact of PTEN loss is therefore linked to the underlying type of genomic abnormality, both in adult and paediatric T-ALLs, demonstrating that detailed analysis of the type of abnormality type would be useful to refine risk stratification.

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Acknowledgements

AT was supported by a grant from INCa (Institut National du Cancer: «Soutien à la Recherche Translationnelle 2012»). MT was supported by Grants from Fondation de France (FdF) and Fondation pour la recherche sur le Cancer (ARC). This work was supported by grants from the ‘La Ligue Contre le Cancer’ and the ‘Association Laurette Fugain’.

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Authors and Affiliations

  1. Institut Necker-Enfants Malades (INEM), Institut national de recherche médicale (INSERM) U1151, Hôpital Necker-Enfants Malades, Paris, France

    M Tesio, A Trinquand, G Hypolite, L Lhermitte, E Macintyre & V Asnafi

  2. Université Paris Descartes Sorbonne Cité and Laboratory of Onco-Hematology, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Necker-Enfants Malades, Paris, France

    A Trinquand, L Lhermitte, E Macintyre & V Asnafi

  3. INSERM, U967, Fontenay-aux-Roses, France

    P Ballerini

  4. Laboratory of Hematology, Hôpital Trousseau, AP-HP, Paris, France

    P Ballerini

  5. Service d’hématologie pédiatrique, AP-HP, Hôpital Trousseau, Paris, France

    A Petit

  6. Pôle de Recherche et d’Enseignement Supérieur L’Université Nantes Angers Le Mans, Centre Hospitalier Universitaire Angers Service des Maladies du Sang et L’Institut National de la Santé et de la Recherche Médicale (INSERM) U892, Angers, France

    N Ifrah

  7. Service d’hématologie pédiatrique, AP-HP, Hôpital Robert Debré, Paris, France

    A Baruchel

  8. Université Paris 7, Hôpital Saint-Louis, AP-HP, and Institut Universitaire d’Hématologie, Paris, France

    H Dombret

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  1. M Tesio
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  4. G Hypolite
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  11. V Asnafi
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Correspondence to V Asnafi.

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Tesio, M., Trinquand, A., Ballerini, P. et al. Age-related clinical and biological features of PTEN abnormalities in T-cell acute lymphoblastic leukaemia. Leukemia 31, 2594–2600 (2017). https://doi.org/10.1038/leu.2017.157

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