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

• Published in: Journal of cellular and molecular medicine 2017-06, Vol.21 (6), p.1237-1242
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Acute myeloid leukemia; Blood platelets; CD34 antigen; Health risks; Leukemia; Mutation; Peripheral blood; Remission; Runx1 protein; Thrombocytopenia
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.13051

Familial platelet disorder with predisposition to acute myeloid leukaemia ( FPD / AML ) is characterized by germline RUNX 1 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 TCR γ 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 CD 34 + 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 TET 2 P1962T mutation in association with germline RUNX 1 R174Q mutation leads to amplification of a haematopoietic clone susceptible to acquire other transforming alterations.