Abstract Number: PB1450
Meeting: ISTH 2020 Congress
Background: ANKRD26-Related Thrombocytopenia (ANKRD26-RT), Familial Platelet Disorder with propensity to Acute Myelogenous Leukemia (FPD/AML), and ETV6-Related Thrombocytopenia (ETV6-RT) are three rare autosomal dominant inherited thrombocytopenias caused by mutations of the ANKRD26, RUNX1, and ETV6 genes, respectively. Since they are associated with an increased risk of developing hematological neoplasms, such as myelodysplastic syndrome, acute myeloid leukemia, and acute lymphoblastic leukemia, they have recently been recognized by the WHO as a unique nosological entity called “myeloid neoplasms with germ line predisposition and preexisting platelet disorder”
Considering that these diseases lack specific pathognomonic signs that could help in differential diagnosis, the screening for mutations of ANKRD26, RUNX1, and ETV6 genes is the only approach available for identifying these patients.
Aims: The main goal of this study was to better characterize these three forms of IT providing insights into their pathogenic mechanisms.
Methods: Mutational screening was perform using a targeted Next Generation Sequencing approach developed in our laboratory for the simultaneous analysis of 28 IT genes.
Functional studies are based on gene reporter assays and immunofluorescence
Results: Since identification of genetic variants does not necessarily confirm the diagnosis because the effect of missense or silent and intronic variants remains of uncertain significance, we have set up – at least for ANKRD26 and ETV6 – luciferase based assay that allow us to identify 5 mutation hiting the 5’UTR of ANKRD26 gene in 44 families and 13 families carrying 6 different mutation on ETV6 gene. Moreover, we performed immunofluorescence assays showing that the mutant ETV6 proteins were unable to enter the nucleus and are retained in the cytoplasm.
Conclusions: Thanks to a consolidated collaboration with IRCCS San Matteo (Pavia, Italy), we have collected one of the largest cohorts of families with ANKRD26-RT, FPD/AML, and ETV6-RT provinding insights on molecular characterization of ANKRD26-RT and ETV6-RT and on pathogenetic mechanism of ETV6 mutations.
To cite this abstract in AMA style:Faleschini M, Papa N, Giangregorio T, Pozzani F, Pecci A, Bozzi V, Barozzi S, Noris P, Marconi C, Seri M, Giona F, Santopietro M, De Benedictis D, Savoia A. Inherited Thrombocytopenia Associated with Haematological Malignancies [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/inherited-thrombocytopenia-associated-with-haematological-malignancies/. Accessed September 27, 2023.
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