Haematologica (Aug 2019)
DNMT3A mutation is associated with increased age and adverse outcome in adult T-cell acute lymphoblastic leukemia
- Jonathan Bond,
- Aurore Touzart,
- Stéphane Leprêtre,
- Carlos Graux,
- Mario Bargetzi,
- Ludovic Lhermitte,
- Guillaume Hypolite,
- Thibaut Leguay,
- Yosr Hicheri,
- Gaëlle Guillerm,
- Karin Bilger,
- Véronique Lhéritier,
- Mathilde Hunault,
- Françoise Huguet,
- Yves Chalandon,
- Norbert Ifrah,
- Elizabeth Macintyre,
- Hervé Dombret,
- Vahid Asnafi,
- Nicolas Boissel
Affiliations
- Jonathan Bond
- Université Paris Descartes Sorbonne Cité, Institut Necker-Enfants Malades (INEM), Institut National de Recherche Médicale (INSERM) U1151, and Laboratory of Onco-Hematology, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Necker Enfants-Malades, Paris, France;Systems Biology Ireland, School of Medicine, University College Dublin, Ireland;National Children’s Research Centre, Children’s Health Ireland at Crumlin, Dublin, Ireland
- Aurore Touzart
- Université Paris Descartes Sorbonne Cité, Institut Necker-Enfants Malades (INEM), Institut National de Recherche Médicale (INSERM) U1151, and Laboratory of Onco-Hematology, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Necker Enfants-Malades, Paris, France
- Stéphane Leprêtre
- INSERM U1245 and Department of Hematology, Centre Henri Becquerel and Normandie Université UNIROUEN, Rouen, France
- Carlos Graux
- Department of Hematology, Université Catholique de Louvain (UCL), Centre Hospitalier Universitaire (CHU) Namur - Godinne site, Yvoir, Belgium
- Mario Bargetzi
- University Medical Department, Division of Oncology, Hematology and Transfusion Medicine, Kantonsspital Aarau, Aarau, Switzerland;Swiss Group for Clinical Cancer Research (SAKK), Bern, Switerland
- Ludovic Lhermitte
- Université Paris Descartes Sorbonne Cité, Institut Necker-Enfants Malades (INEM), Institut National de Recherche Médicale (INSERM) U1151, and Laboratory of Onco-Hematology, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Necker Enfants-Malades, Paris, France
- Guillaume Hypolite
- Université Paris Descartes Sorbonne Cité, Institut Necker-Enfants Malades (INEM), Institut National de Recherche Médicale (INSERM) U1151, and Laboratory of Onco-Hematology, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Necker Enfants-Malades, Paris, France
- Thibaut Leguay
- Department of Hematology, CHU de Bordeaux, France
- Yosr Hicheri
- Hematology Service, Hôpital St Eloi, Montpellier, France
- Gaëlle Guillerm
- Hematology Service, CHU de Brest, Brest, France
- Karin Bilger
- Hematology Service, CHU Hautepierre, Strasbourg, France
- Véronique Lhéritier
- Group for Research on Adult Acute Lymphoblastic Leukemia, Coordination Office, Centre Hospitalier Lyon Sud, Lyon, France
- Mathilde Hunault
- PRES LUNAM, CHU Angers Service des Maladies du Sang and CRCINA INSERM, Angers, France
- Françoise Huguet
- Department of Hematology, CHU de Toulouse, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse, France
- Yves Chalandon
- University Medical Department, Division of Oncology, Hematology and Transfusion Medicine, Kantonsspital Aarau, Aarau, Switzerland;Department of Oncology, Hematology Division, University Hospital, Geneva, Switzerland
- Norbert Ifrah
- PRES LUNAM, CHU Angers Service des Maladies du Sang and CRCINA INSERM, Angers, France
- Elizabeth Macintyre
- Université Paris Descartes Sorbonne Cité, Institut Necker-Enfants Malades (INEM), Institut National de Recherche Médicale (INSERM) U1151, and Laboratory of Onco-Hematology, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Necker Enfants-Malades, Paris, France
- Hervé Dombret
- Université Paris Diderot, Institut Universitaire d’Hématologie, EA-3518, AP-HP, University Hospital Saint-Louis, Paris, France
- Vahid Asnafi
- Université Paris Descartes Sorbonne Cité, Institut Necker-Enfants Malades (INEM), Institut National de Recherche Médicale (INSERM) U1151, and Laboratory of Onco-Hematology, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Necker Enfants-Malades, Paris, France
- Nicolas Boissel
- Université Paris Diderot, Institut Universitaire d’Hématologie, EA-3518, AP-HP, University Hospital Saint-Louis, Paris, France
- DOI
- https://doi.org/10.3324/haematol.2018.197848
- Journal volume & issue
-
Vol. 104,
no. 8
Abstract
The prognostic implications of DNMT3A genotype in T-cell acute lymphoblastic leukemia are incompletely understood. We performed comprehensive genetic and clinico-biological analyses of T-cell acute lymphoblastic leukemia patients with DNMT3A mutations treated during the GRAALL-2003 and -2005 studies. Eighteen of 198 cases (9.1%) had DNMT3A alterations. Two patients also had DNMT3A mutations in non-leukemic cell DNA, providing the first potential evidence of age-related clonal hematopoiesis in T-cell acute lymphoblastic leukemia. DNMT3A mutation was associated with older age (median 43.9 years vs. 29.4 years, P
