First description of revertant mosaicism in familial platelet disorder with predisposition to acute myelogenous leukemia: correlation with the clinical phenotype
- Autores
- Glembotsky, Ana Claudia; Marin Oyarzún, Cecilia Paola; de Luca, Geraldine; Marzac, Christophe; Auger, Nathalie; Goette, Nora Paula; Marta, Rosana Fernanda; Raslova, Hana; Heller, Paula Graciela
- Año de publicación
- 2020
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- 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 - Materia
-
Familial platelet disorder with predisposition to acute myelogenous leukemia
Platelets
RUNX1
Mosaicism - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/130477
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First description of revertant mosaicism in familial platelet disorder with predisposition to acute myelogenous leukemia: correlation with the clinical phenotypeGlembotsky, Ana ClaudiaMarin Oyarzún, Cecilia Paolade Luca, GeraldineMarzac, ChristopheAuger, NathalieGoette, Nora PaulaMarta, Rosana FernandaRaslova, HanaHeller, Paula GracielaFamilial platelet disorder with predisposition to acute myelogenous leukemiaPlateletsRUNX1Mosaicismhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Familial 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; ArgentinaFil: 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; ArgentinaFil: 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; ArgentinaFil: Marzac, Christophe. Inserm; FranciaFil: Auger, Nathalie. Inserm; FranciaFil: 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; ArgentinaFil: 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; ArgentinaFil: Raslova, Hana. Inserm; FranciaFil: 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; ArgentinaFerrata Storti Foundation2020-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/130477Glembotsky, Ana Claudia; Marin Oyarzún, Cecilia Paola; de Luca, Geraldine; Marzac, Christophe; Auger, Nathalie; et al.; First description of revertant mosaicism in familial platelet disorder with predisposition to acute myelogenous leukemia: correlation with the clinical phenotype; Ferrata Storti Foundation; Haematologica; 105; 10; 10-2020; 535-5391592-8721CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.haematologica.org/lookup/doi/10.3324/haematol.2020.253070info:eu-repo/semantics/altIdentifier/doi/10.3324/haematol.2020.253070info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:51:36Zoai:ri.conicet.gov.ar:11336/130477instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:51:37.136CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
First description of revertant mosaicism in familial platelet disorder with predisposition to acute myelogenous leukemia: correlation with the clinical phenotype |
title |
First description of revertant mosaicism in familial platelet disorder with predisposition to acute myelogenous leukemia: correlation with the clinical phenotype |
spellingShingle |
First description of revertant mosaicism in familial platelet disorder with predisposition to acute myelogenous leukemia: correlation with the clinical phenotype Glembotsky, Ana Claudia Familial platelet disorder with predisposition to acute myelogenous leukemia Platelets RUNX1 Mosaicism |
title_short |
First description of revertant mosaicism in familial platelet disorder with predisposition to acute myelogenous leukemia: correlation with the clinical phenotype |
title_full |
First description of revertant mosaicism in familial platelet disorder with predisposition to acute myelogenous leukemia: correlation with the clinical phenotype |
title_fullStr |
First description of revertant mosaicism in familial platelet disorder with predisposition to acute myelogenous leukemia: correlation with the clinical phenotype |
title_full_unstemmed |
First description of revertant mosaicism in familial platelet disorder with predisposition to acute myelogenous leukemia: correlation with the clinical phenotype |
title_sort |
First description of revertant mosaicism in familial platelet disorder with predisposition to acute myelogenous leukemia: correlation with the clinical phenotype |
dc.creator.none.fl_str_mv |
Glembotsky, Ana Claudia Marin Oyarzún, Cecilia Paola de Luca, Geraldine Marzac, Christophe Auger, Nathalie Goette, Nora Paula Marta, Rosana Fernanda Raslova, Hana Heller, Paula Graciela |
author |
Glembotsky, Ana Claudia |
author_facet |
Glembotsky, Ana Claudia Marin Oyarzún, Cecilia Paola de Luca, Geraldine Marzac, Christophe Auger, Nathalie Goette, Nora Paula Marta, Rosana Fernanda Raslova, Hana Heller, Paula Graciela |
author_role |
author |
author2 |
Marin Oyarzún, Cecilia Paola de Luca, Geraldine Marzac, Christophe Auger, Nathalie Goette, Nora Paula Marta, Rosana Fernanda Raslova, Hana Heller, Paula Graciela |
author2_role |
author author author author author author author author |
dc.subject.none.fl_str_mv |
Familial platelet disorder with predisposition to acute myelogenous leukemia Platelets RUNX1 Mosaicism |
topic |
Familial platelet disorder with predisposition to acute myelogenous leukemia Platelets RUNX1 Mosaicism |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
dc.description.none.fl_txt_mv |
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 |
description |
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. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-10 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/130477 Glembotsky, Ana Claudia; Marin Oyarzún, Cecilia Paola; de Luca, Geraldine; Marzac, Christophe; Auger, Nathalie; et al.; First description of revertant mosaicism in familial platelet disorder with predisposition to acute myelogenous leukemia: correlation with the clinical phenotype; Ferrata Storti Foundation; Haematologica; 105; 10; 10-2020; 535-539 1592-8721 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/130477 |
identifier_str_mv |
Glembotsky, Ana Claudia; Marin Oyarzún, Cecilia Paola; de Luca, Geraldine; Marzac, Christophe; Auger, Nathalie; et al.; First description of revertant mosaicism in familial platelet disorder with predisposition to acute myelogenous leukemia: correlation with the clinical phenotype; Ferrata Storti Foundation; Haematologica; 105; 10; 10-2020; 535-539 1592-8721 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/url/http://www.haematologica.org/lookup/doi/10.3324/haematol.2020.253070 info:eu-repo/semantics/altIdentifier/doi/10.3324/haematol.2020.253070 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Ferrata Storti Foundation |
publisher.none.fl_str_mv |
Ferrata Storti Foundation |
dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) |
collection |
CONICET Digital (CONICET) |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.name.fl_str_mv |
CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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1842269105775706112 |
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13.13397 |