title: Acquired TET2 mutation in one patient with familial platelet disorder with predisposition to AML led to the development of pre-leukaemic clone resulting in T2-ALL and AML-M0.
abstract: Familial platelet disorder with predisposition to acute myeloid leukaemia (FPD/AML) is characterized by germline RUNX1 mutations, thrombocytopaenia, platelet dysfunction and a risk of developing acute myeloid and in rare cases lymphoid T leukaemia. Here, we focus on a case of a man with a familial history of RUNX1R174Qmutation who developed at the age of 42 years a T2-ALL and, 2 years after remission, an AML-M0. Both AML-M0 and T2-ALL blast populations demonstrated a loss of 1p36.32-23 and 17q11.2 regions as well as other small deletions, clonal rearrangements of both TCRγ and TCRδ and a presence of 18 variants at a frequency of more than 40%. Additional variants were identified only in T2-ALL or in AML-M0 evoking the existence of a common original clone, which gave rise to subclonal populations. Next generation sequencing (NGS) performed on peripheral blood-derived CD34+cells 5 years prior to T2-ALL development revealed only the missense TET2P1962Tmutation at a frequency of 1%, which increases to more than 40% in fully transformed leukaemic T2-ALL and AML-M0 clones. This result suggests that TET2P1962Tmutation in association with germline RUNX1R174Qmutation leads to amplification of a haematopoietic clone susceptible to acquire other transforming alterations.
authors.affiliation: INSERM UMR 1170, Gustave Roussy, Université Paris-Saclay, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Villejuif, France.|Université Paris Diderot, Paris, France.
authors.forename: Vladimir T
authors.initials: VT
authors.lastname: Manchev
authors.affiliation: INSERM UMR 1170, Gustave Roussy, Université Paris-Saclay, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Villejuif, France.|Université Paris Diderot, Paris, France.
authors.forename: Hind
authors.initials: H
authors.lastname: Bouzid
authors.affiliation: INSERM UMR 1170, Gustave Roussy, Université Paris-Saclay, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Villejuif, France.
authors.forename: Iléana
authors.initials: I
authors.lastname: Antony-Debré
authors.affiliation: Gustave Roussy, Université Paris-Saclay, Genomic Platform UMS AMMICA, Villejuif, France.
authors.forename: Betty
authors.initials: B
authors.lastname: Leite
authors.affiliation: Gustave Roussy, Université Paris-Saclay, Bioinformatic Core Facility UMS AMMICA, Villejuif, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Meurice
authors.affiliation: INSERM UMR 1170, Gustave Roussy, Université Paris-Saclay, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Villejuif, France.|Gustave Roussy, Université Paris-Saclay, Genomic Platform UMS AMMICA, Villejuif, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Droin
authors.affiliation: Faculté de Médecine, Aix-Marseille Université, Marseille, France.|Département d'Hématologie, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Prebet
authors.affiliation: Assistance Publique-Hôpitaux de Marseille, Hôpital de La Conception, Service d'Hématologie et Thérapie Cellulaire, Faculté de Médecine, Aix-Marseille Université, INSERM UMR 1090 TAGC, Marseille, France.
authors.forename: Régis T
authors.initials: RT
authors.lastname: Costello
authors.affiliation: INSERM UMR 1170, Gustave Roussy, Université Paris-Saclay, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Villejuif, France.
authors.forename: William
authors.initials: W
authors.lastname: Vainchenker
authors.affiliation: INSERM UMR 1170, Gustave Roussy, Université Paris-Saclay, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Villejuif, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Plo
authors.affiliation: INSERM UMR 1170, Gustave Roussy, Université Paris-Saclay, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Villejuif, France.|Gustave Roussy, Université Paris-Saclay, Bioinformatic Core Facility UMS AMMICA, Villejuif, France.
authors.forename: M'boyba
authors.initials: M
authors.lastname: Diop
authors.affiliation: Hematology and INSERM U1151, Institut Necker-Enfants Malades, Université Sorbonne Paris Cité, Descartes and Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Macintyre
authors.affiliation: Hematology and INSERM U1151, Institut Necker-Enfants Malades, Université Sorbonne Paris Cité, Descartes and Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Vahid
authors.initials: V
authors.lastname: Asnafi
authors.affiliation: INSERM UMR 1170, Gustave Roussy, Université Paris-Saclay, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Villejuif, France.|Assistance Publique-Hôpitaux de Paris, Hôpital Trousseau, Service d'Hématologie biologique, Paris, France.
authors.forename: Rémi
authors.initials: R
authors.lastname: Favier
authors.affiliation: Assistance Publique-Hôpitaux de Marseille, Hôpital Nord, Laboratoire d'Hématologie, Faculté de Médecine, Aix-Marseille Université, INSERM UMR_S 1062, Marseille, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Baccini
authors.affiliation: INSERM UMR 1170, Gustave Roussy, Université Paris-Saclay, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Villejuif, France.
authors.forename: Hana
authors.initials: H
authors.lastname: Raslova
mesh_terms: D000328:Adult; D018952:Antigens, CD34 / Q000235:genetics; D001791:Blood Platelet Disorders / Q000150:complications / Q000235:genetics* / Q000473:pathology; D001792:Blood Platelets / Q000473:pathology; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D049308:Dioxygenases; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000150:complications / Q000235:genetics* / Q000473:pathology; D008297:Male; D011518:Proto-Oncogene Proteins / Q000235:genetics*
chemical_list: D018952:Antigens, CD34; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; C493728:RUNX1 protein, human; D049308:Dioxygenases; C541081:TET2 protein, human
keywords: AML-M0; FPD/AML; RUNX1; T2-ALL; TET2; predisposition to leukaemia