Mutations of RUNX1 in families with inherited thrombocytopenia
| Autor: | De Rocco, Daniela, Melazzini, Federica, Marconi, Caterina, Pecci, Alessandro, Bottega, Roberta, Gnan, Chiara, Palombo, Flavia, Giordano, Paola Florencia, Coccioli, Maria Susanna, Glembotsky, Ana Claudia, Heller, Paula Graciela, Seri, Marco, Savoia, Anna, Noris, Patrizia |
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| Přispěvatelé: | De Rocco, Daniela, Melazzini, Federica, Marconi, Caterina, Pecci, Alessandro, Bottega, Roberta, Gnan, Chiara, Palombo, Flavia, Giordano, Paola, Coccioli, Maria Susanna, Glembotsky, Ana C., Heller, Paula G., Seri, Marco, Savoia, Anna, Noris, Patrizia, DE ROCCO, Daniela |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Adult
Blood Platelets Male Transcriptional Activation Heterozygote RUNX1 CIENCIAS MÉDICAS Y DE LA SALUD myeloid neoplasm Mutation Missense Medicina Clínica Young Adult Protein Domains hemic and lymphatic diseases Humans Child Frameshift Mutation Cell Size Genes Dominant Sequence Deletion INHERITED THROMBOCYTOPENIA platelet disorder Hematology Middle Aged Introns Leukemia Myeloid Acute RUNX1 gene Thrombopoietin Child Preschool Core Binding Factor Alpha 2 Subunit Female Medicina Critica y de Emergencia RNA Splice Sites FPD/AML LEUKEMIA Thrombocythemia Essential |
| Popis: | Familial platelet disorder with propensity to myeloid malignancy (FPD/AML) is a rare autosomal dominant form of thrombocytopenia associated with an increased risk of myelodysplastic syndrome and acute myeloid leukemia (AML) caused by germline mutations in the hematopoietic transcription factor RUNX1. Molecular testing allowed us to identify mutations in 13 individuals from three families with inherited thrombocytopenia (IT). They had thrombocytopenia with platelet normal volume and variable expressivity of other morphological and functional defects of platelets, such as reduction of alpha-granules and expression of GPIa-IIa, decreased aggregation, increased level of serum thrombopoietin. In this cohort, only three patients developed AML, with an incidence relative lower than that reported in literature. Since this discrepancy could be explained by different criteria of enrolment (RUNX1 is regarded as a candidate gene only when thrombocytopenia is associated with AML), a systematic screening of RUNX1 in IT families would allow us to identify carriers and more precisely determine the leukemic risk. Yet, considering that recognition of families with FPD/AML is of fundamental importance in the choice of donors for hematopoietic stem cell transplantation, current recommendation includes molecular genetic testing of genes (RUNX1 but also ANKRD26, and ETV6) whose mutations not only are responsible for thrombocytopenia with normal platelet volume but also increase the risk of hematological cancers. Fil: De Rocco, Daniela. Institute for Maternal and Child Healt; Italia Fil: Melazzini, Federica. Policlinico San Matteo Foundation; Italia. University of Pavia; Italia Fil: Marconi, Caterina. Universidad de Bologna; Italia Fil: Pecci, Alessandro. Policlinico San Matteo Foundation; Italia. University of Pavia; Italia Fil: Bottega, Roberta. Università degli Studi di Trieste; Italia Fil: Gnan, Chiara. Institute for Maternal and Child Healt; Italia Fil: Palombo, Flavia. Universidad de Bologna; Italia Fil: Giordano, Paola Florencia. Universita Degli Studi Di Bari; Italia Fil: Coccioli, Maria Susanna. Hospital “D. Camberlingo; Italia Fil: Glembotsky, Ana Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Heller, Paula Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Seri, Marco. Universidad de Bologna; Italia Fil: Savoia, Anna. Università degli Studi di Trieste; Italia. Institute for Maternal and Child Healt; Italia Fil: Noris, Patrizia. University of Pavia; Italia |
| Databáze: | OpenAIRE |
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