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, thrombocy-topaenia, 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 TCRc and TCRd 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 sequen-cing (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.
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Journal of Cellular and Molecular Medicine, Wiley Open Access, 2017, 21 (6), pp.1237 - 1242. 〈10.1111/jcmm.13051〉
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Vladimir T. Manchev, Hind Bouzid, Iléana Antony-Debré, Betty Leite, Guillaume Meurice, et al.. 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. Journal of Cellular and Molecular Medicine, Wiley Open Access, 2017, 21 (6), pp.1237 - 1242. 〈10.1111/jcmm.13051〉. 〈hal-01537098〉

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