Insights into the clinical, platelet and genetic landscape of inherited thrombocytopenia with malignancy risk
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.
Authors
- Nuria Revilla (ORCID: https://orcid.org/0000-0002-0995-1043)
- Francisca Ferrer‐Marín (ORCID: https://orcid.org/0000-0002-9520-3243)
- Cristina Sierra‐Aisa (ORCID: https://orcid.org/0000-0001-7328-8955)
- Jorge Huerta‐Aragonés (ORCID: https://orcid.org/0000-0002-9209-6657)
- Ana Sánchez‐Fuentes (ORCID: https://orcid.org/0000-0002-4656-4771)
- Ana Zamora‐Cánovas (ORCID: https://orcid.org/0000-0002-5562-203X)
- Teresa Sevivas
- Agustín Rodríguez‐Alén (ORCID: https://orcid.org/0000-0003-3583-2977)
- Lorena Díaz‐Ajenjo (ORCID: https://orcid.org/0000-0003-0716-385X)
- Irene Peláez‐Pleguezuelos
- Jordi Esteve (ORCID: https://orcid.org/0000-0002-8056-648X)
- Nuria Fernández‐Mosteirín
- Monica López‐Duarte (ORCID: https://orcid.org/0000-0001-8134-9682)
- José María Bastida (ORCID: https://orcid.org/0000-0002-8007-3909)
- Raquel de Oña
- Luis Hernández Encinas (ORCID: https://orcid.org/0000-0001-6980-2683)
- José Ramón González‐Porras (ORCID: https://orcid.org/0000-0003-3266-7996)
- Antônio Ponce de León (ORCID: https://orcid.org/0000-0002-0704-5215)
- Elena Sebastián (ORCID: https://orcid.org/0000-0002-5444-8076)
- José Rivera (ORCID: https://orcid.org/0000-0003-4225-6840)
- Meritxell Nomdedéu (ORCID: https://orcid.org/0000-0002-2839-3577)
- Fernando Ramos (ORCID: https://orcid.org/0000-0002-4991-2655)
- Rosa Vidal‐Laso
- Mónica Martín‐Salces (ORCID: https://orcid.org/0000-0001-6380-5023)
- Thais Murciano
- Rocío Benito (ORCID: https://orcid.org/0000-0001-9781-4198)
- Nora Butta (ORCID: https://orcid.org/0000-0003-4601-7150)
- Ana Marín‐Quilez (ORCID: https://orcid.org/0000-0002-2005-1919)
- Marı́a Luisa Lozano (ORCID: https://orcid.org/0000-0003-3148-7037)
- Claudia Serrano (ORCID: https://orcid.org/0000-0002-9688-6162)
- Laura Murillo (ORCID: https://orcid.org/0000-0001-6925-260X)
- P. Martín Escribano
- Rosa María Píriz Campos
- Pedro Luis Gómez‐González (ORCID: https://orcid.org/0009-0007-6103-7236)
- Eugenia López (ORCID: https://orcid.org/0000-0002-7820-4068)
Institutions
- Universidad Complutense de Madrid (ES)
- Universidad de Salamanca (ES)
- Hospital Universitario La Paz (ES)
- Hospitais da Universidade de Coimbra (PT)
- Hospital General Universitario Gregorio Marañón (ES)
- Universidad Nuestra Señora de La Paz (BO)
- Hospital de Basurto (ES)
- Vall d'Hebron Institut de Recerca (ES)
- Hospital Infantil Universitario Niño Jesús (ES)
- Instituto de Investigación Marqués de Valdecilla (ES)
- Hospital Universitario Miguel Servet (ES)
- Hospital Clínic de Barcelona (ES)
- Centro Regional de Hemodonación (ES)
- Hospital General Universitario de Elche (ES)
- Hospital Universitario Virgen de las Nieves (ES)
- Hospital Universitario Fundación Jiménez Díaz (ES)
- Hospital Materno-Infantil (ES)
- Instituto de Investigación Biomédica de Salamanca (ES)
- Hospital de Cruces (ES)
- Centro de Investigación del Cáncer (ES)
- Hospital Universitario Virgen de la Arrixaca (ES)
- Hospital Jerez Puerta del Sur (ES)
- MD Anderson Cancer Center Madrid (ES)
- Complejo Hospitalario Universitario de Toledo (ES)
- Complejo Asistencial Universitario de Palencia (ES)
- Universidad Autónoma de Madrid (ES)
Publication Details
- Journal
- British Journal of Haematology
- Published
- 2025-07-16
- DOI
- https://doi.org/10.1111/bjh.70001
- Citations
- 4
- Primary Topic
- Blood disorders and treatments
- Type
- article
- Field-Weighted Citation Impact
- 7.27
Funders
- European Commission
- Sociedad Española de Hematología y Hemoterapia
- Junta de Castilla y León
- Instituto de Salud Carlos III