1. WT1 gene is overexpressed in myeloproliferative neoplasms, especially in myelofibrosis
- Author
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Anne Bouvier, Valérie Ugo, Anaïse Blouet, Alain Zannetti, Mathilde Hunault-Berger, Matgorzata Truchan-Graczyk, Jérémie Riou, Damien Luque Paz, Odile Blanchet, Laurane Cottin, Annaëlle Beucher, Corentin Orvain, Françoise Boyer, Rébecca Jouanneau-Courville, Bénédicte Ribourtout, Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Laboratoire d'Hématologie [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Fédérations hospitalo-universitaires Grand Ouest Acute Leukemia [Angers] (FHU GOAL), Micro et Nanomédecines Translationnelles (MINT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Service des maladies du sang [CHU Angers], Hématologie clinique [CH Cholet], CH Cholet, Hématologie clinique [CH Saumur], Centre Hospitalier de Saumur - CH Saumur, UFR Santé [UNIV Angers], Université d'Angers (UA), Centre de Ressources Biologiques [CHU d'Angers] (CRB CHU d'Angers BB-0033-00038), This work is part of the French clinical and biological network of myeloproliferative neoplasms (FIMBANK) supported by a grant from the Institut National du Cancer (INCa BCB 2013)., Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Bernardo, Elizabeth
- Subjects
Adult ,0301 basic medicine ,congenital, hereditary, and neonatal diseases and abnormalities ,Myelofibrosis ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,urologic and male genital diseases ,Myeloproliferative neoplasms ,03 medical and health sciences ,0302 clinical medicine ,Polycythemia vera ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,Neoplasms ,hemic and lymphatic diseases ,Gene expression ,Humans ,Medicine ,RNA, Messenger ,WT1 Proteins ,Polycythemia Vera ,Molecular Biology ,Aged ,Aged, 80 and over ,Myeloproliferative Disorders ,urogenital system ,business.industry ,Essential thrombocythemia ,Hematopoietic Stem Cell Transplantation ,Myeloid leukemia ,Cell Biology ,Hematology ,Middle Aged ,Allografts ,medicine.disease ,Minimal residual disease ,female genital diseases and pregnancy complications ,WT1 ,Transplantation ,Leukemia, Myeloid, Acute ,030104 developmental biology ,ROC Curve ,Primary Myelofibrosis ,Cancer research ,Molecular Medicine ,Stem cell ,business ,Thrombocythemia, Essential ,030215 immunology - Abstract
International audience; Classical Philadelphia-negative myeloproliferative neoplasms include Polycythemia Vera (PV), Essential Thrombocythemia (ET) and Primary Myelofibrosis (PMF). They are characterized by the presence of driver mutations of JAK2, CALR or MPL genes. Overexpression of WT1 is used as a marker of minimal residual disease in acute myeloid leukemia, especially after allogeneic stem cell transplantation (SCT). We investigated WT1 expression at diagnosis in 152 MPN patients and showed that the WT1 transcript was overexpressed in PMFs and PVs compared to controls. In particular, WT1 transcript levels were higher in PMF than in ET and PV. WT1 transcript levels were significantly increased during myelofibrotic transformation of ET or PV. Using multi-variate linear regression, high WT1 transcript levels in PMF were associated with age over 65, splenomegaly and thrombocytopenia. The ROC curve analysis showed that a level of WT1 transcript > 10 WT1 copies/10 4 ABL1 enabled the diagnosis of PMF with a specificity of 95.8% (PMF vs ET; ROC AUC = 0.91). In myelofibrosis, studying follow-ups of WT1 transcript showed that this marker is of interest after allogeneic SCT. These results demonstrate that WT1 overexpression is a simple marker of myelofibrosis in MPN and could be used during patient follow-up.
- Published
- 2019