First description of revertant mosaicism in familial platelet disorder with predisposition to acute myelogenous leukemia: correlation with the clinical phenotype
| Autor: | Geraldine De Luca, Rosana F. Marta, Cecilia Paola Marin Oyarzún, Nathalie Auger, Hana Raslova, Ana C. Glembotsky, Paula G. Heller, Christophe Marzac, Nora Paula Goette |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Platelets
RUNX1 Platelet disorder Revertant Case Reports chemistry.chemical_compound Myelogenous Humans Medicine Familial platelet disorder with predisposition to acute myelogenous leukemia Clinical phenotype business.industry Mosaicism Hematology purl.org/becyt/ford/3.1 [https] medicine.disease Leukemia Myeloid Acute Leukemia Inherited platelet disorder Phenotype chemistry Immunology purl.org/becyt/ford/3 [https] Blood Platelet Disorders business |
| Zdroj: | CONICET Digital (CONICET) Consejo Nacional de Investigaciones Científicas y Técnicas instacron:CONICET Haematologica |
| Popis: | Familial platelet disorder with predisposition to acute myelogenous leukemia (FPD/AML) is an autosomal dominant condition characterized by abnormal platelet number and function and 30-60% risk of hematologic malignancies, including myelodysplastic syndrome, acute myelogenous leukemia and T-cell lymphoblastic leukemia.1 It is caused by heterozygous germline muta- tions in the gene encoding the transcription factor RUNX1, which is essential in the emergence of definitive hematopoiesis and plays a key role in the lymphoid and megakaryocyte lineages.1,2 RUNX1 mutations predispose to leukemia by inducing genomic instability which favors the acquisition of secondary somatic mutations.3 Thrombocytopenia is mild to moderate with normal- sized platelets and most patients display a platelet func- tion defect with impaired platelet aggregation and dense- granule deficiency.1 However, the platelet phenotype is heterogeneous4 and even normal platelet count and func- tion have been reported in rare carriers of RUNX1 muta- tions,5 highlighting that the diagnosis may be overlooked. Dysregulated expression of RUNX1-targets in platelets, including downregulation of the α2 subunit (GPIa) of col- lagen receptor α2b16 or persistent myosin 10 (MYH10) expression,7 have been proposed as screening tools to guide diagnosis, although it is at present unknown whether all FPD/AML patients harbor these defects. Therefore, molecular screening is still required to ade- quately identify RUNX1 mutation carriers.We report the finding of genetic mosaicism in a patient belonging to a well-characterized FPD/AML pedigree and describe the relationship between molecular and clinical features over a 12-year follow-up. Fil: Glembotsky, Ana Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Marin Oyarzún, Cecilia Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: de Luca, Geraldine. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Marzac, Christophe. Inserm; Francia Fil: Auger, Nathalie. Inserm; Francia Fil: Goette, Nora Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Marta, Rosana Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Raslova, Hana. Inserm; Francia Fil: Heller, Paula Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina |
| Databáze: | OpenAIRE |
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