1. Clinical and molecular response to interferon-α therapy in essential thrombocythemia patients with CALR mutations
- Author
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Serge Carillo, Aurélie Chauveau, Stéphane Giraudier, Jean-Jacques Kiladjian, Emmanuelle Verger, Valérie Ugo, Mohammed A. Yassin, Bruno Cassinat, Christine Chomienne, Marie-Hélène Schlageter, Jean-Christophe Ianotto, Eric Legouffe, Nader Al-Dewik, Christine Dosquet, Unite de Biologie Cellulaire (Biol Cell - ST LOUIS - PARIS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire d'hématologie (Labo Hémato - BREST), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Unité de Formation de Recherche de Médecine (UFRM - BREST), Université de Brest (UBO), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire d'hématologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut de cancérologie et d'hématologie, Hôpital Morvan [Brest]-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Department of Hematology and Bone Marrow Transplant (DHBMT - DOHA - QATAR), National Center for Cancer Care and Research (NCCCR - DOHA - QATAR), Qatar Medical Genetic Center (QMGC - DOHA - QATAR), Hamad medical corporation, Département de Cytologie Clinique (Dep Cyto Clin - NIMES), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service d'hématologie et oncologie médicale, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie-Université de Montpellier (UM), ONCOGARD - NIMES, Institut de Cancérologie du GARD ICG - CHU Nîmes (Instit Cancéro - GARD), Université d'Angers - Faculté de médecine (UA UFR Médecine), Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Laboratoire d'Hématologie Biologique (Hémato - ANGERS), Centre Hospitalier Universitaire d'Angers (CHU Angers), Hématologie -Immunologie -Cibles thérapeutiques, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigations Cliniques, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Lapeyronie-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), and Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
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Male ,Oncology ,[SDV]Life Sciences [q-bio] ,DNA Mutational Analysis ,Gene mutation ,medicine.disease_cause ,Biochemistry ,Somatic evolution in cancer ,Polyethylene Glycols ,0302 clinical medicine ,Hydroxyurea ,interferon-a therapy ,0303 health sciences ,Mutation ,essential thrombocythemia ,biology ,Remission Induction ,Hematology ,Middle Aged ,Isocitrate Dehydrogenase ,Recombinant Proteins ,3. Good health ,DNA-Binding Proteins ,030220 oncology & carcinogenesis ,Female ,Thrombocythemia, Essential ,CALR mutations ,Adult ,medicine.medical_specialty ,Adolescent ,Immunology ,Alpha interferon ,IDH2 ,Dioxygenases ,Clonal Evolution ,Young Adult ,03 medical and health sciences ,Proto-Oncogene Proteins ,Internal medicine ,medicine ,Humans ,Allele ,Alleles ,030304 developmental biology ,Aspirin ,Essential thrombocythemia ,Interferon-alpha ,Off-Label Use ,Cell Biology ,Genes, p53 ,medicine.disease ,Clone Cells ,Repressor Proteins ,biology.protein ,Calreticulin ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,Follow-Up Studies - Abstract
International audience; Myeloproliferative neoplasms are clonal disorders characterized by the presence of several gene mutations associated with particular hematologic parameters, clinical evolution, and prognosis. Few therapeutic options are available, among which interferon α (IFNα) presents interesting properties like the ability to induce hematologic responses (HRs) and molecular responses (MRs) in patients with JAK2 mutation. We report on the response to IFNα therapy in a cohort of 31 essential thrombocythemia (ET) patients with CALR mutations (mean follow-up of 11.8 years). HR was achieved in all patients. Median CALR mutant allelic burden (%CALR) significantly decreased from 41% at baseline to 26% after treatment, and 2 patients even achieved complete MR. In contrast, %CALR was not significantly modified in ET patients treated with hydroxyurea or aspirin only. Next-generation sequencing identified additional mutations in 6 patients (affecting TET2, ASXL1, IDH2, and TP53 genes). The presence of additional mutations was associated with poorer MR on CALR mutant clones, with only minor or no MRs in this subset of patients. Analysis of the evolution of the different variant allele frequencies showed that the mutated clones had a differential sensitivity to IFNα in a given patient, but no new mutation emerged during treatment. In all, this study shows that IFNα induces high rates of HRs and MRs in CALR-mutated ET, and that the presence of additional nondriver mutations may influence the MR to therapy.
- Published
- 2015
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