title: Response to 5-azacytidine in a patient with TET2-mutated angioimmunoblastic T-cell lymphoma and chronic myelomonocytic leukaemia preceded by an EBV-positive large B-cell lymphoma.
abstract: We report the case of a patient with a history of Epstein-Barr virus-positive large B-cell lymphoma, who relapsed with an angioimmunoblastic T-cell lymphoma (AITL) associated with a chronic myelomonocytic leukaemia (CMML). We performed targeted next-generation sequencing on CMML and AITL DNA, which revealed mutations of TET2, DNMT3A, SRSF2, NRAS and IDH1, thus confirming that the spectrum of AITL mutations share similarities with myeloid disorders. The frequencies of TET2/DNMT3A and SRSF2 variants could support the hypothesis that TET2/DNMT3A mutations occurred in an early progenitor cell, which later progressed to both the AITL and CMML clones. Treatment with 5-azacytidine led to the complete remission of both diseases. Thus, targeting DNA methylation abnormalities in AITL may be an alternative strategy to chemotherapy. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Clinical Hematology, IMAGINE Institute, Paris Descartes-Sorbonne Paris Cité University, Necker Hospital, AP-HP, Paris, France.
authors.forename: Colombe
authors.initials: C
authors.lastname: Saillard
authors.affiliation: Biological Hematology, Paris Descartes-Sorbonne Paris Cité University, Cochin Hospital, AP-HP, Paris, France.
authors.forename: Helene
authors.initials: H
authors.lastname: Guermouche
authors.affiliation: Biological Hematology, Paris Descartes-Sorbonne Paris Cité University, Necker Hospital, AP-HP, Paris, France.
authors.forename: Coralie
authors.initials: C
authors.lastname: Derrieux
authors.affiliation: Department of Pathology, Imagine Institute, Paris Descartes-Sorbonne Paris Cité University, Necker Hospital, AP-HP, Paris, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Bruneau
authors.affiliation: Clinical Hematology, IMAGINE Institute, Paris Descartes-Sorbonne Paris Cité University, Necker Hospital, AP-HP, Paris, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Frenzel
authors.affiliation: Clinical Hematology, IMAGINE Institute, Paris Descartes-Sorbonne Paris Cité University, Necker Hospital, AP-HP, Paris, France.|INSERM UMR 1163 and CNRS ERL 8254, Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutical Implications, Imagine Institute, Paris, France.
authors.forename: Lucile
authors.initials: L
authors.lastname: Couronne
authors.affiliation: Biological Hematology, Paris Descartes-Sorbonne Paris Cité University, Necker Hospital, AP-HP, Paris, France.
authors.forename: Vahid
authors.initials: V
authors.lastname: Asnafi
authors.affiliation: Biological Hematology, Paris Descartes-Sorbonne Paris Cité University, Necker Hospital, AP-HP, Paris, France.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Macintyre
authors.affiliation: Biological Hematology, Paris Descartes-Sorbonne Paris Cité University, Necker Hospital, AP-HP, Paris, France.
authors.forename: Amélie
authors.initials: A
authors.lastname: Trinquand
authors.affiliation: Biological Hematology, Paris Descartes-Sorbonne Paris Cité University, Necker Hospital, AP-HP, Paris, France.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Lhermitte
authors.affiliation: Department of Pathology, Imagine Institute, Paris Descartes-Sorbonne Paris Cité University, Necker Hospital, AP-HP, Paris, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Molina
authors.affiliation: Clinical Hematology, IMAGINE Institute, Paris Descartes-Sorbonne Paris Cité University, Necker Hospital, AP-HP, Paris, France.|INSERM UMR 1163 and CNRS ERL 8254, Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutical Implications, Imagine Institute, Paris, France.
authors.forename: Felipe
authors.initials: F
authors.lastname: Suarez
authors.affiliation: Clinical Hematology, IMAGINE Institute, Paris Descartes-Sorbonne Paris Cité University, Necker Hospital, AP-HP, Paris, France.
authors.forename: Francois
authors.initials: F
authors.lastname: Lemonnier
authors.affiliation: Biological Hematology, Paris Descartes-Sorbonne Paris Cité University, Cochin Hospital, AP-HP, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Kosmider
authors.affiliation: Clinical Hematology, IMAGINE Institute, Paris Descartes-Sorbonne Paris Cité University, Necker Hospital, AP-HP, Paris, France.|INSERM UMR 1163 and CNRS ERL 8254, Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutical Implications, Imagine Institute, Paris, France.
authors.forename: Richard
authors.initials: R
authors.lastname: Delarue
authors.affiliation: Clinical Hematology, IMAGINE Institute, Paris Descartes-Sorbonne Paris Cité University, Necker Hospital, AP-HP, Paris, France.|INSERM UMR 1163 and CNRS ERL 8254, Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutical Implications, Imagine Institute, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Hermine
authors.affiliation: Clinical Hematology, IMAGINE Institute, Paris Descartes-Sorbonne Paris Cité University, Necker Hospital, AP-HP, Paris, France.|INSERM UMR 1163 and CNRS ERL 8254, Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutical Implications, Imagine Institute, Paris, France.
authors.forename: Morgane
authors.initials: M
authors.lastname: Cheminant
mesh_terms: D000369:Aged, 80 and over; D001374:Azacitidine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D015477:Leukemia, Myelomonocytic, Chronic / Q000188:drug therapy* / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000209:etiology*; D016399:Lymphoma, T-Cell / Q000188:drug therapy* / Q000473:pathology
chemical_list: D001374:Azacitidine
keywords: Angioimmunoblastic T-cell lymphoma; DNA methylation; EBV; TET2; azacytidine