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. Issue 6 (20th December 2016)

• Record Type: Journal Article
• 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
• Is Part Of: Journal of cellular and molecular medicine. Volume 21:Issue 6(2017)
• Page Start: 1237
• Page End: 1242
• Publication Date: 2016-12-20
• Subjects: FPD/AML -- predisposition to leukaemia -- RUNX1 -- TET2 -- AML‐M0 -- T2‐ALL; Cytology; Medicine; Molecular Biology; Cytologie -- Périodiques; Médecine -- Périodiques; Biologie moléculaire -- Périodiques; Cytology -- Periodicals; Medicine -- Periodicals; Molecular biology -- Periodicals; 611.01805
• DOI: 10.1111/jcmm.13051
• Languages: English
• ISSNs: 1582-1838

Abstract

Abstract: 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.