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.

Autor: Manchev VT; INSERM UMR 1170, Gustave Roussy, Université Paris-Saclay, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Villejuif, France.; Université Paris Diderot, Paris, France., Bouzid H; INSERM UMR 1170, Gustave Roussy, Université Paris-Saclay, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Villejuif, France.; Université Paris Diderot, Paris, France., Antony-Debré I; INSERM UMR 1170, Gustave Roussy, Université Paris-Saclay, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Villejuif, France., Leite B; Gustave Roussy, Université Paris-Saclay, Genomic Platform UMS AMMICA, Villejuif, France., Meurice G; Gustave Roussy, Université Paris-Saclay, Bioinformatic Core Facility UMS AMMICA, Villejuif, France., Droin N; 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., Prebet T; Faculté de Médecine, Aix-Marseille Université, Marseille, France.; Département d'Hématologie, Institut Paoli-Calmettes, Marseille, France., Costello RT; 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., Vainchenker W; INSERM UMR 1170, Gustave Roussy, Université Paris-Saclay, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Villejuif, France., Plo I; INSERM UMR 1170, Gustave Roussy, Université Paris-Saclay, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Villejuif, France., Diop M; 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., Macintyre E; Hematology and INSERM U1151, Institut Necker-Enfants Malades, Université Sorbonne Paris Cité, Descartes and Assistance Publique-Hôpitaux de Paris, Paris, France., Asnafi V; Hematology and INSERM U1151, Institut Necker-Enfants Malades, Université Sorbonne Paris Cité, Descartes and Assistance Publique-Hôpitaux de Paris, Paris, France., Favier R; 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., Baccini V; Assistance Publique-Hôpitaux de Marseille, Hôpital Nord, Laboratoire d'Hématologie, Faculté de Médecine, Aix-Marseille Université, INSERM UMR_S 1062, Marseille, France., Raslova H; INSERM UMR 1170, Gustave Roussy, Université Paris-Saclay, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Villejuif, France.
Jazyk: angličtina
Zdroj: Journal of cellular and molecular medicine [J Cell Mol Med] 2017 Jun; Vol. 21 (6), pp. 1237-1242. Date of Electronic Publication: 2016 Dec 20.
DOI: 10.1111/jcmm.13051
Abstrakt: 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 RUNX1 R174Q mutation 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 TET2 P1962T mutation 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 TET2 P1962T mutation in association with germline RUNX1 R174Q mutation leads to amplification of a haematopoietic clone susceptible to acquire other transforming alterations.
(© 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)
Databáze: MEDLINE
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