20.500.12556/DiRROS-27897 Disease characteristics and outcomes of acute myeloidleukemia in germline RUNX1 deficiency (Familial Platelet Disorder with associated Myeloid Malignancy) Familial Platelet Disorder with associated Myeloid Malignancy (FPDMM, FPD/AML, RUNX1-FPD), caused by monoallelic deleterious germline RUNX1 variants, is characterized by bleeding diathesis and predisposition for hematologic malignancies, particularly myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Clinical data on FPDMM-associated AML (FPDMM-AML) are limited, complicating evidence-based clinical decision-making. Here, we present retrospective genetic and clinical data of the largest cohort of FPDMM patients reported to date. We describe 159 European patients (from 94 families) of whom 134 were evaluable for the development of malignant disease. Sixty developed a hematologic malignancy (44.8%), most frequently AML (36/134, 26.9%) or MDS (18/134, 13.4%). Somatic alterations of RUNX1 by gene mutation (48%) and chromosome 21 aberrations (14.3%) were the most common somatic genetic aberrations in FPDMM-AML, followed by FLT3-ITD mutations (24.1%). Somatic RUNX1 and FLT3-ITD mutations were not detected in FPDMM-associated MDS, suggesting important contributions to leukemic transformation. Remission-induction chemotherapy resulted in complete remission in 80% of FPDMM-AML patients with a 5-year overall survival (OS) of 50.4%. Survival outcome was non-inferior compared to a large cohort of newly diagnosed adult RUNX1-mutated AML (5-year OS 36.6%, p = 0.5), with relatively infrequent concurrent adverse risk somatic aberrations (ASXL1 mutation, monosomal karyotype, monosomy 5/del 5q) in FPDMM-AML. Collectively, data support the notion that step-wise leukemic evolution in FPDMM is associated with distinct genetic events and indicate that a substantial subset of FPDMM-AML patients achieves prolonged survival with conventional AML treatment, including allogeneic stem cell transplant. These findings are anticipated to inform personalized clinical decision-making in this rare disorder acute myeloidleukemia Familial Platelet Disorder true false true Angleški jezik Ni določen Neznano 2026-02-27 09:34:00 2026-02-27 09:34:00 2026-02-28 04:20:52 0000-00-00 00:00:00 2025 0 0 Nasl. z nasl. zaslona; Opis z dne 30. 4. 2025; str. 1-13 iss. 1 Vol. 9 2025 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 61 2572-9241 10.1002/hem3.70057 234614019 RAZ_Ernst_Martijn_P._T._2025.pdf RAZ_Ernst_Martijn_P._T._2025.pdf 1 060BFD70E2484846C262274D34721F15 2b4c911567512024f7379bbeb649308459f05b1bbd36dae2da7a0a356af5962d 3b5e8a55-13b7-11f1-8c73-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=41067 https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70057 1 12ff2acd-13b7-11f1-8c73-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=41066 Univerzitetni klinični center Ljubljana 0 0 0