Acute lymphoblastic leukemia

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

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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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Correspondence to V Asnafi.

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The authors declare no conflict of interest.

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Supplementary Information accompanies this paper on the Leukemia website

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