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


  • Manchev Vladimir T.
  • Bouzid Hind
  • Antony-Debré Iléana
  • Leite Betty
  • Meurice Guillaume
  • Droin Nathalie
  • Prebet Thomas
  • Costello Régis T.
  • Vainchenker William
  • Plo Isabelle
  • Diop M'Boyba
  • Macintyre Elizabeth
  • Asnafi Vahid
  • Favier Rémi
  • Baccini Véronique
  • Raslova Hana

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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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