Clinical and pathogenic features of ETV6-related thrombocytopenia with predisposition to acute lymphoblastic leukemia
| Autor: | Serena Barozzi, Giuseppe Loffredo, Carlo L. Balduini, Chiara Gnan, Alessandra Balduini, Caterina Marconi, Michael Doubek, Lenka Radová, Christian A. Di Buduo, Federica Melazzini, Caterina Alfano, Anna Savoia, Daniela De Rocco, Valeria Bozzi, Tommaso Pippucci, Flavia Palombo, Marco Seri, Michela Faleschini, Katerina Stano Kozubik, Patrizia Noris, Šárka Pospíšilová, Alessandro Pecci |
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| Přispěvatelé: | Melazzini, Federica, Palombo, Flavia, Balduini, Alessandra, DE ROCCO, Daniela, Marconi, Caterina, Noris, Patrizia, Gnan, Chiara, Pippucci, Tommaso, Bozzi, Valeria, Faleschini, Michela, Barozzi, Serena, Doubek, Michael, Di Buduo, Christian A., Kozubik, Katerina Stano, Radova, Lenka, Loffredo, Giuseppe, Pospisilova, Sarka, Alfano, Caterina, Seri, Marco, Balduini, Carlo L., Pecci, Alessandro, Savoia, Anna, De Rocco, Daniela, Di Buduo, Christian A, Stano Kozubik, Katerina, Balduini, Carlo L |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Fibrinogen 0302 clinical medicine hemic and lymphatic diseases Medicine Platelet platelet disorders inherited thrombocytopenia Child inherited thrombocytopenias education.field_of_study Hematology Incidence (epidemiology) Nuclear Proteins Middle Aged Precursor Cell Lymphoblastic Leukemia-Lymphoma Pedigree 3. Good health Cell Transformation Neoplastic Child Preschool Core Binding Factor Alpha 2 Subunit Cohort Intercellular Signaling Peptides and Proteins medicine.drug Adult Platelets medicine.medical_specialty Adolescent Platelet disorder Population Article Young Adult 03 medical and health sciences Internal medicine Humans Family Genetic Predisposition to Disease education Proto-Oncogene Proteins c-ets business.industry Infant Newborn Infant Thrombocytopenia Repressor Proteins ETV6 030104 developmental biology Mutation Immunology business 030215 immunology |
| Zdroj: | Melazzini, F, Palombo, F, Balduini, A, De Rocco, D, Marconi, C, Noris, P, Gnan, C, Pippucci, T, Bozzi, V, Faleschini, M, Barozzi, S, Doubek, M, Di Buduo, C A, Stano Kozubik, K, Radova, L, Loffredo, G, Pospisilova, S, Alfano, C, Seri, M, Balduini, C L, Pecci, A & Savoia, A 2016, ' Clinical and pathogenetic features of ETV6 related thrombocytopenia with predisposition to acute lymphoblastic leukemia ', Haematologica . https://doi.org/10.3324/haematol.2016.147496 |
| Popis: | ETV6-related thrombocytopenia is an autosomal dominant thrombocytopenia that has been recently identified in a few families and has been suspected to predispose to hematologic malignancies. To gain further information on this disorder, we searched for ETV6 mutations in the 130 families with inherited thrombocytopenia of unknown origin from our cohort of 274 consecutive pedigrees with familial thrombocytopenia. We identified 20 patients with ETV6-related thrombocytopenia from seven pedigrees. They have five different ETV6 variants, including three novel mutations affecting the highly conserved E26 transformation-specific domain. The relative frequency of ETV6-related thrombocytopenia was 2.6% in the whole case series and 4.6% among the families with known forms of inherited thrombocytopenia. The degree of thrombocytopenia and bleeding tendency of the patients with ETV6-related thrombocytopenia were mild, but four subjects developed B-cell acute lymphoblastic leukemia during childhood, resulting in a significantly higher incidence of this condition compared to that in the general population. Clinical and laboratory findings did not identify any particular defects that could lead to the suspicion of this disorder from the routine diagnostic workup. However, at variance with most inherited thrombocytopenias, platelets were not enlarged. In vitro studies revealed that the maturation of the patients' megakaryocytes was defective and that the patients have impaired proplatelet formation. Moreover, platelets from patients with ETV6-related thrombocytopenia have reduced ability to spread on fibrinogen. Since the dominant thrombocytopenias due to mutations in RUNX1 and ANKRD26 are also characterized by normal platelet size and predispose to hematologic malignancies, we suggest that screening for ETV6, RUNX1 and ANKRD26 mutations should be performed in all subjects with autosomal dominant thrombocytopenia and normal platelet size. |
| Databáze: | OpenAIRE |
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