2026-04-17T01:00:24Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/138632025-10-24T08:49:53Zcom_2072_378070com_2072_378040com_2072_378071col_2072_378092col_2072_378097

00925njm 22002777a 4500 dc Marin-Quilez, Ana author SÁNCHEZ FUENTES, ANA author Zamora Cánovas, Ana author Gómez-González, Pedro Luis author Diaz-Ajenjo, Lorena author BENITO SANCHEZ, M ROCIO author Murciano, Thais author Murillo-Sanjuán, Laura author 2025-10-15T11:12:55Z 2025-10-15T11:12:55Z 2025-10 Inherited thrombocytopenia; Malignancy predisposition Trombocitopenia hereditaria; Predisposición a malignidad Trombocitopènia hereditària; Predisposició a malignitat Inherited thrombocytopenia (IT) with germline variants in RUNX1, ETV6 or ANKRD26 carries a high risk (10%–45%) of developing haematological malignancy (IT-HM). We evaluated the clinical, platelet and molecular characteristics in 37 patients with RUNX1-related thrombocytopenia (RT), 9 with ETV6-RT and 20 with ANRKD26-RT. Genetic diagnosis was delayed by about 20 years from the identification of thrombocytopenia. Bleeding tendency was present in 25%–30% of RUNX1-RT and ANKRD26-RT patients. Platelet aggregation was impaired in 90% of all patients, while reduced activation and granule secretion were heterogeneous. Most RUNX1-RT patients had low glycoprotein Ia (GPIa) levels, which may be a useful disease biomarker. Sixteen distinct genetic variants in RUNX1, four in ETV6 and four in ANKRD26 were identified in patients. The clinical profile showed immune, skin, gastrointestinal and other comorbidities in many patients. One third of the cases developed a malignancy: This included eight RUNX1-RT patients with myelodysplastic syndrome (MDS), five with acute myeloid leukaemia (AML), and one with chronic myeloid leukaemia (CML) Ph+. One patient with ETV6-RT subsequently developed B-cell acute lymphoblastic leukaemia (B-ALL) during childhood. Three cases with ANKRD26-RT demonstrated a multifaceted clinical presentation, including B-ALL Ph+, MDS and breast cancer. The high incidence of HM development highlights the importance of early diagnosis in life. This work was supported by grants from: Instituto de Salud Carlos III (ISCIII) & European Union (PI23/00624, PI24/01458); ISCIII & European Union- NextGeneration EU and for PRTR (PMP21/00052); CIBERER-ISCIII (CB15/00055); Fundación Séneca- Agencia de Ciencia y Tecnología de la Región de Murcia (21 920/PI/22); Gerencia Regional de Salud (GRS2551/A/22, GRS2907/A1/2023, GRS2727/A1/23); Sociedad Española de Trombosis y Hemostasia (SETH, Premio López Borrasca, Ayuda a Grupos de Trabajo & Beca Dr. Francisco España, 2024); and Real Fundación Victoria Eugenia (Premio Investigación 2023). AM-Q is funded by ‘Ayuda postdoctoral from Sociedad Española de Hematología y Hemoterapia (SEHH)’ and Ministerio de Ciencia, Innovación y Universidades-Programa Juan de la Cierva (JDC2023-052518-I). AS-F and AZ-C hold training grants from ISCIII (Rio Hortega CM23/00028, FI21/00157). LD-A holds a fellowship from Junta de Castilla y León (JCYL-EDU/1868/2022). The authors' research on Inherited Platelet Disorders is conducted in accordance with the objectives of the project ‘Functional and Molecular Characterization of Patients with Inherited Platelet Disorders’ of the Grupo Español de Alteraciones Plaquetarias Congénitas (GEAPC), supported by SETH. http://hdl.handle.net/11351/13863 Sang - Càncer - Aspectes genètics Trombocitopènia - Aspectes genètics Sang - Càncer - Propensió DISEASES::Hemic and Lymphatic Diseases::Hematologic Diseases::Blood Platelet Disorders::Thrombocytopenia Other subheadings::Other subheadings::Other subheadings::/genetics DISEASES::Neoplasms::Neoplasms by Site::Hematologic Neoplasms PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Mutation::Germ-Line Mutation ENFERMEDADES::enfermedades hematológicas y linfáticas::enfermedades hematológicas::trastornos de las plaquetas sanguíneas::trombocitopenia Otros calificadores::Otros calificadores::Otros calificadores::/genética ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias hematológicas FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::mutación::mutación de la línea germinal Insights into the clinical, platelet and genetic landscape of inherited thrombocytopenia with malignancy risk