Five new pedigrees with inherited RUNX1 mutations causing familial platelet disorder with propensity to myeloid malignancy
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- 1 December 2008
- journal article
- case report
- Published by American Society of Hematology in Blood
- Vol. 112 (12), 4639-4645
- https://doi.org/10.1182/blood-2008-05-156745
Abstract
Familial platelet disorder with propensity to myeloid malignancy (FPD/AML) is an autosomal dominant syndrome characterized by platelet abnormalities and a predisposition to myelodysplasia (MDS) and/or acute myeloid leukemia (AML). The disorder, caused by inherited mutations in RUNX1, is uncommon with only 14 pedigrees reported. We screened 10 families with a history of more than one first degree relative with MDS/AML for inherited mutations in RUNX1. Germ- line RUNX1 mutations were identified in 5 pedigrees with a 3:2 predominance of N-terminal mutations. Several affected members had normal platelet counts or platelet function, features not previously reported in FPD/AML. The median incidence of MDS/AML among carriers of RUNX1 mutation was 35%. Individual treatments varied but included hematopoietic stem cell transplantation from siblings before recognition of the inherited leukemogenic mutation. Transplantation was associated with a high incidence of complications including early relapse, failure of engraftment, and posttransplantation lymphoproliferative disorder. Given the small size of modern families and the clinical heterogeneity of this syndrome, the diagnosis of FPD/AML could be easily overlooked and may be more prevalent than previously recognized. Therefore, it would appear prudent to screen young patients with MDS/AML for RUNX1 mutation, before consideration of sibling hematopoietic stem cell transplantation.Keywords
This publication has 22 references indexed in Scilit:
- A novel RUNX1 mutation in familial platelet disorder with propensity to develop myeloid malignanciesHaematologica, 2008
- Low Mpl receptor expression in a pedigree with familial platelet disorder with predisposition to acute myelogenous leukemia and a novel AML1 mutationBlood, 2005
- Point mutation in AML1 disrupts subnuclear targeting, prevents myeloid differentiation, and effects a transformation-like phenotypeProceedings of the National Academy of Sciences of the United States of America, 2005
- Point mutations in the RUNX1/AML1 gene: another actor in RUNX leukemiaOncogene, 2004
- High incidence of somatic mutations in the AML1/RUNX1 gene in myelodysplastic syndrome and low blast percentage myeloid leukemia with myelodysplasiaBlood, 2004
- Association of CBFA2 mutation with decreased platelet PKC-θ and impaired receptor-mediated activation of GPIIb-IIIa and pleckstrin phosphorylation: proteins regulated by CBFA2 play a role in GPIIb-IIIa activationBlood, 2004
- Implications of somatic mutations in the AML1 gene in radiation-associated and therapy-related myelodysplastic syndrome/acute myeloid leukemiaBlood, 2003
- In vitro analyses of known and novel RUNX1/AML1 mutations in dominant familial platelet disorder with predisposition to acute myelogenous leukemia: implications for mechanisms of pathogenesisBlood, 2002
- Buccal swabs but not mouthwash samples can be used to obtain pretransplant DNA fingerprints from recipients of allogeneic bone marrow transplantsBone Marrow Transplantation, 2000
- Haploinsufficiency of CBFA2 causes familial thrombocytopenia with propensity to develop acute myelogenous leukaemiaNature Genetics, 1999