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Acquired TET 2 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

2016; Wiley; Volume: 21; Issue: 6 Linguagem: Inglês

10.1111/jcmm.13051

1582-4934

Vladimir T. Manchev, Hind Bouzid, Iléana Antony‐Debré, Betty Leite, Guillaume Meurice, Nathalie Droin, Thomas Prébet, Régis Costello, William Vainchenker, Isabelle Plo, M’Boyba Diop, Elizabeth Macintyre, Vahid Asnafi, Rémi Favier, Véronique Baccini, Hana Raslová,

Chronic Myeloid Leukemia Treatments

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 RUNX1R174Q 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 TET2P1962T 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 TET2P1962T mutation in association with germline RUNX1R174Q mutation leads to amplification of a haematopoietic clone susceptible to acquire other transforming alterations.