Toward a NOTCH1/FBXW7/RAS/PTEN-based oncogenetic risk classification of adult T-cell acute lymphoblastic leukemia: a Group for Research in Adult Acute Lymphoblastic Leukemia study.

Autor:	Trinquand A; Amélie Trinquand, Raouf Ben Abdelali, Etienne Lengliné, Noémie De Gunzburg, Ludovic Lhermitte, Jonathan Bond, Agnès Buzyn, Elizabeth Macintyre, and Vahid Asnafi, University Paris Descartes, Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR)-8147, and Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Necker-Enfants Malades; Jérôme Lambert, UMR-S-717, Hôpital Saint-Louis, AP-HP; Kheira Beldjord, Etienne Lengliné, and Hervé Dombret, University Paris 7, Hôpital Saint-Louis, AP-HP, and Institut Universitaire d'Hématologie, EA3518, Paris; Aline Tanguy-Schmidt and Norbert Ifrah, 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; Dominique Payet-Bornet and Bertrand Nadel, Center of Immunology of Marseille Luminy, Aix-Marseille University, INSERM U1104 and Centre National de la Recherche Scientifique (CNRS) UMR-7280, Marseille; Hossein Mossafa, Laboratoire Cerba, Cergy-Pontoise; Véronique Lhéritier and Xavier Thomas, Centre Hospitalier Lyon Sud, Lyon; Françoise Huguet, Hôpital Purpan, Toulouse; Thibaud Leguay, Centre Hospitalier du Haut Lévêque, Pessac; Jean-Yves Cahn, UMR-5525 CNRS-Université Joseph Fourier, Grenoble; Caroline Bonmati, Centre Hospitalier Régional Hôpital de Brabois, Vandoeuvre Les Nancy; Sebastien Maury, Hôpital Henry Mondor, Creteil, France; Yves Chalandon, University Hospital of Geneva, Geneva, Switzerland; and André Delannoy, Hopital de Jolimont, La Louviere, Belgium., Tanguy-Schmidt A, Ben Abdelali R, Lambert J, Beldjord K, Lengliné E, De Gunzburg N, Payet-Bornet D, Lhermitte L, Mossafa H, Lhéritier V, Bond J, Huguet F, Buzyn A, Leguay T, Cahn JY, Thomas X, Chalandon Y, Delannoy A, Bonmati C, Maury S, Nadel B, Macintyre E, Ifrah N, Dombret H, Asnafi V
Jazyk:	angličtina
Zdroj:	Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2013 Dec 01; Vol. 31 (34), pp. 4333-42. Date of Electronic Publication: 2013 Oct 28.
DOI:	10.1200/JCO.2012.48.5292
Abstrakt:	Purpose: The Group for Research in Adult Acute Lymphoblastic Leukemia (GRAALL) recently reported a significantly better outcome in T-cell acute lymphoblastic leukemia (T-ALL) harboring NOTCH1 and/or FBXW7 (N/F) mutations compared with unmutated T-ALL. Despite this, one third of patients with N/F-mutated T-ALL experienced relapse. Patients and Methods: In a series of 212 adult T-ALLs included in the multicenter randomized GRAALL-2003 and -2005 trials, we searched for additional N/K-RAS mutations and PTEN defects (mutations and gene deletion). Results: N/F mutations were identified in 143 (67%) of 212 patients, and lack of N/F mutation was confirmed to be associated with a poor prognosis. K-RAS, N-RAS, and PTEN mutations/deletions were identified in three (1.6%) of 191, 17 (8.9%) of 191, and 21 (12%) of 175 patients, respectively. The favorable prognostic significance of N/F mutations was restricted to patients without RAS/PTEN abnormalities. These observations led us to propose a new T-ALL oncogenetic classifier defining low-risk patients as those with N/F mutation but no RAS/PTEN mutation (97 of 189 patients; 51%) and all other patients (49%; including 13% with N/F and RAS/PTEN mutations) as high-risk patients. In multivariable analysis, this oncogenetic classifier remained the only significant prognostic covariate (event-free survival: hazard ratio [HR], 3.2; 95% CI, 1.9 to 5.15; P < .001; and overall survival: HR, 3.2; 95% CI, 1.9 to 5.6; P < .001). Conclusion: These data demonstrate that the presence of N/F mutations in the absence of RAS or PTEN abnormalities predicts good outcome in almost 50% of adult T-ALL. Conversely, the absence of N/F or presence of RAS/PTEN alterations identifies the remaining cohort of patients with poor prognosis.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu