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
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/130477
Acceder
id CONICETDig_d7df707ce552444b57d8fbeeaa81ab7c
oai_identifier_str oai:ri.conicet.gov.ar:11336/130477
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling 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 Técnicas2025-09-29T09:48:06Zoai: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:34982025-09-29 09:48:06.227CONICET 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
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str 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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score 13.070432

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