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We evaluated the clinical, platelet and molecular characteristics in 37 patients with RUNX1\u2010related thrombocytopenia (RT), 9 with ETV6\u2010RT and 20 with ANRKD26\u2010RT. Genetic diagnosis was delayed by about 20\u2009years from the identification of thrombocytopenia. Bleeding tendency was present in 25%\u201330% of RUNX1\u2010RT and ANKRD26\u2010RT patients. Platelet aggregation was impaired in 90% of all patients, while reduced activation and granule secretion were heterogeneous. Most RUNX1\u2010RT patients had low glycoprotein Ia (GPIa) levels, which may be a useful disease biomarker. Sixteen distinct genetic variants in <jats:italic>RUNX1<\/jats:italic>, four in <jats:italic>ETV6<\/jats:italic> and four in <jats:italic>ANKRD26<\/jats:italic> 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\u2010RT patients with myelodysplastic syndrome (MDS), five with acute myeloid leukaemia (AML), and one with chronic myeloid leukaemia (CML) Ph+. One patient with ETV6\u2010RT subsequently developed B\u2010cell acute lymphoblastic leukaemia (B\u2010ALL) during childhood. Three cases with ANKRD26\u2010RT demonstrated a multifaceted clinical presentation, including B\u2010ALL Ph+, MDS and breast cancer. The high incidence of HM development highlights the importance of early diagnosis in life.<\/jats:p>","DOI":"10.1111\/bjh.70001","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T05:44:28Z","timestamp":1752731068000},"page":"1565-1577","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Insights into the clinical, platelet and genetic landscape of inherited thrombocytopenia with malignancy risk"],"prefix":"10.1111","volume":"207","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2005-1919","authenticated-orcid":false,"given":"Ana","family":"Mar\u00edn\u2010Qu\u00edlez","sequence":"first","affiliation":[{"name":"Servicio de Hematolog\u00eda, Centro Regional de Hemodonaci\u00f3n, IMIB\u2010Pascual Parrilla, CIBERER\u2010ISCIII, Hospital Universitario Morales Meseguer Universidad de Murcia  Murcia 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