Somatic mutations associated with leukemic progression of familial platelet disorder with predisposition to acute myeloid leukemia

Autores
Antony Debré, I.; Duployez, N.; Bucci, M.; Geffroy, S.; Micol, J.-B.; Renneville, A.; Boissel, N.; Dhédin, N.; Réa, D.; Nelken, B.; Berthon, C.; Leblanc, T.; Mozziconacci, M. J.; Favier, R.; Heller, Paula Graciela; Abdel Wahab, O.; Raslova, H.; Latger Cannard, V.; Preudhomme, C.
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML) represents a unique model to study leukemic progression. Whereas qualitative or quantitative platelet defects are a constant feature of the disease, the onset of the hematological malignancy can be very heterogeneous and the molecular mechanisms responsible for leukemia progression remain poorly understood. We analyzed a cohort of 25 individuals from 15 FPD/AML pedigrees for mutations in 44 AML-associated genes, including genes recently associated with germline or acquired RUNX1 aberrations such as CDC25C, GATA2 and ASXL1/2. Of the 25 patients, 13 were studied following acute leukemia development (10 with acute myeloid leukemia (AML) and 3 with T-cell acute lymphoblastic leukemia). Interestingly, a second, somatically acquired alteration in RUNX1 was found in nearly all patients who developed AML, including second mutation, copy neutral loss of heterozygosity or duplication of the RUNX1-mutated or -deleted allele. These latter two events were identified by analysis of the allelic ratio coupled with karyotype. Additional somatic mutations in genes implicated in signaling, RNA splicing or epigenetic regulation were also identified at leukemic transformation. Our findings suggest that biallelic RUNX1 alterations are crucial for AML development in FPD/AML.
Fil: Antony Debré, I.. Albert Einstein College of Medicine; Estados Unidos. Université de Paris XI; Francia
Fil: Duployez, N.. University Lille Nord; Francia. Inserm; Francia
Fil: Bucci, M.. University Lille Nord; Francia
Fil: Geffroy, S.. University Lille Nord; Francia. Inserm; Francia
Fil: Micol, J.-B.. Université de Paris XI; Francia. Inserm; Francia. Weill Cornell Medical College; Estados Unidos
Fil: Renneville, A.. University Lille Nord; Francia. Inserm; Francia
Fil: Boissel, N.. Université Paris Diderot - Paris 7; Francia
Fil: Dhédin, N.. Université Paris Diderot - Paris 7; Francia
Fil: Réa, D.. Université Paris Diderot - Paris 7; Francia
Fil: Nelken, B.. CHU of Lille. Department of Pediatric Hematology; Francia
Fil: Berthon, C.. Inserm; Francia. CHU of Lille. Department of Pediatric Hematology; Francia
Fil: Leblanc, T.. Hôpital Robert Debré; Francia
Fil: Mozziconacci, M. J.. Institut Paoli-Calmettes; Francia
Fil: Favier, R.. Inserm; Francia. Hôpital Trousseau; Francia. Université de Paris XI; Francia
Fil: Heller, Paula Graciela. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina. 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: Abdel Wahab, O.. Weill Cornell Medical College; Estados Unidos. Memorial Sloan-Kettering Cancer Center; Estados Unidos
Fil: Raslova, H.. Inserm; Francia. Université de Paris XI; Francia
Fil: Latger Cannard, V.. Nancy University Hospital; Francia
Fil: Preudhomme, C.. Inserm; Francia. University Lille Nord; Francia
Materia
Runx1
Leukemia
Platelet
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:11336/39326
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/39326
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Somatic mutations associated with leukemic progression of familial platelet disorder with predisposition to acute myeloid leukemiaAntony Debré, I.Duployez, N.Bucci, M.Geffroy, S.Micol, J.-B.Renneville, A.Boissel, N.Dhédin, N.Réa, D.Nelken, B.Berthon, C.Leblanc, T.Mozziconacci, M. J.Favier, R.Heller, Paula GracielaAbdel Wahab, O.Raslova, H.Latger Cannard, V.Preudhomme, C.Runx1LeukemiaPlatelethttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3The familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML) represents a unique model to study leukemic progression. Whereas qualitative or quantitative platelet defects are a constant feature of the disease, the onset of the hematological malignancy can be very heterogeneous and the molecular mechanisms responsible for leukemia progression remain poorly understood. We analyzed a cohort of 25 individuals from 15 FPD/AML pedigrees for mutations in 44 AML-associated genes, including genes recently associated with germline or acquired RUNX1 aberrations such as CDC25C, GATA2 and ASXL1/2. Of the 25 patients, 13 were studied following acute leukemia development (10 with acute myeloid leukemia (AML) and 3 with T-cell acute lymphoblastic leukemia). Interestingly, a second, somatically acquired alteration in RUNX1 was found in nearly all patients who developed AML, including second mutation, copy neutral loss of heterozygosity or duplication of the RUNX1-mutated or -deleted allele. These latter two events were identified by analysis of the allelic ratio coupled with karyotype. Additional somatic mutations in genes implicated in signaling, RNA splicing or epigenetic regulation were also identified at leukemic transformation. Our findings suggest that biallelic RUNX1 alterations are crucial for AML development in FPD/AML.Fil: Antony Debré, I.. Albert Einstein College of Medicine; Estados Unidos. Université de Paris XI; FranciaFil: Duployez, N.. University Lille Nord; Francia. Inserm; FranciaFil: Bucci, M.. University Lille Nord; FranciaFil: Geffroy, S.. University Lille Nord; Francia. Inserm; FranciaFil: Micol, J.-B.. Université de Paris XI; Francia. Inserm; Francia. Weill Cornell Medical College; Estados UnidosFil: Renneville, A.. University Lille Nord; Francia. Inserm; FranciaFil: Boissel, N.. Université Paris Diderot - Paris 7; FranciaFil: Dhédin, N.. Université Paris Diderot - Paris 7; FranciaFil: Réa, D.. Université Paris Diderot - Paris 7; FranciaFil: Nelken, B.. CHU of Lille. Department of Pediatric Hematology; FranciaFil: Berthon, C.. Inserm; Francia. CHU of Lille. Department of Pediatric Hematology; FranciaFil: Leblanc, T.. Hôpital Robert Debré; FranciaFil: Mozziconacci, M. J.. Institut Paoli-Calmettes; FranciaFil: Favier, R.. Inserm; Francia. Hôpital Trousseau; Francia. Université de Paris XI; FranciaFil: Heller, Paula Graciela. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina. 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: Abdel Wahab, O.. Weill Cornell Medical College; Estados Unidos. Memorial Sloan-Kettering Cancer Center; Estados UnidosFil: Raslova, H.. Inserm; Francia. Université de Paris XI; FranciaFil: Latger Cannard, V.. Nancy University Hospital; FranciaFil: Preudhomme, C.. Inserm; Francia. University Lille Nord; FranciaNature Publishing Group2016-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/39326Antony Debré, I.; Duployez, N.; Bucci, M.; Geffroy, S.; Micol, J.-B.; et al.; Somatic mutations associated with leukemic progression of familial platelet disorder with predisposition to acute myeloid leukemia; Nature Publishing Group; Leukemia; 30; 4; 4-2016; 999-10020887-6924CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/leu2015236info:eu-repo/semantics/altIdentifier/doi/10.1038/leu.2015.236info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:11:23Zoai:ri.conicet.gov.ar:11336/39326instacron: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 10:11:24.162CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Somatic mutations associated with leukemic progression of familial platelet disorder with predisposition to acute myeloid leukemia
title Somatic mutations associated with leukemic progression of familial platelet disorder with predisposition to acute myeloid leukemia
spellingShingle Somatic mutations associated with leukemic progression of familial platelet disorder with predisposition to acute myeloid leukemia
Antony Debré, I.
Runx1
Leukemia
Platelet
title_short Somatic mutations associated with leukemic progression of familial platelet disorder with predisposition to acute myeloid leukemia
title_full Somatic mutations associated with leukemic progression of familial platelet disorder with predisposition to acute myeloid leukemia
title_fullStr Somatic mutations associated with leukemic progression of familial platelet disorder with predisposition to acute myeloid leukemia
title_full_unstemmed Somatic mutations associated with leukemic progression of familial platelet disorder with predisposition to acute myeloid leukemia
title_sort Somatic mutations associated with leukemic progression of familial platelet disorder with predisposition to acute myeloid leukemia
dc.creator.none.fl_str_mv Antony Debré, I.
Duployez, N.
Bucci, M.
Geffroy, S.
Micol, J.-B.
Renneville, A.
Boissel, N.
Dhédin, N.
Réa, D.
Nelken, B.
Berthon, C.
Leblanc, T.
Mozziconacci, M. J.
Favier, R.
Heller, Paula Graciela
Abdel Wahab, O.
Raslova, H.
Latger Cannard, V.
Preudhomme, C.
author Antony Debré, I.
author_facet Antony Debré, I.
Duployez, N.
Bucci, M.
Geffroy, S.
Micol, J.-B.
Renneville, A.
Boissel, N.
Dhédin, N.
Réa, D.
Nelken, B.
Berthon, C.
Leblanc, T.
Mozziconacci, M. J.
Favier, R.
Heller, Paula Graciela
Abdel Wahab, O.
Raslova, H.
Latger Cannard, V.
Preudhomme, C.
author_role author
author2 Duployez, N.
Bucci, M.
Geffroy, S.
Micol, J.-B.
Renneville, A.
Boissel, N.
Dhédin, N.
Réa, D.
Nelken, B.
Berthon, C.
Leblanc, T.
Mozziconacci, M. J.
Favier, R.
Heller, Paula Graciela
Abdel Wahab, O.
Raslova, H.
Latger Cannard, V.
Preudhomme, C.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Runx1
Leukemia
Platelet
topic Runx1
Leukemia
Platelet
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML) represents a unique model to study leukemic progression. Whereas qualitative or quantitative platelet defects are a constant feature of the disease, the onset of the hematological malignancy can be very heterogeneous and the molecular mechanisms responsible for leukemia progression remain poorly understood. We analyzed a cohort of 25 individuals from 15 FPD/AML pedigrees for mutations in 44 AML-associated genes, including genes recently associated with germline or acquired RUNX1 aberrations such as CDC25C, GATA2 and ASXL1/2. Of the 25 patients, 13 were studied following acute leukemia development (10 with acute myeloid leukemia (AML) and 3 with T-cell acute lymphoblastic leukemia). Interestingly, a second, somatically acquired alteration in RUNX1 was found in nearly all patients who developed AML, including second mutation, copy neutral loss of heterozygosity or duplication of the RUNX1-mutated or -deleted allele. These latter two events were identified by analysis of the allelic ratio coupled with karyotype. Additional somatic mutations in genes implicated in signaling, RNA splicing or epigenetic regulation were also identified at leukemic transformation. Our findings suggest that biallelic RUNX1 alterations are crucial for AML development in FPD/AML.
Fil: Antony Debré, I.. Albert Einstein College of Medicine; Estados Unidos. Université de Paris XI; Francia
Fil: Duployez, N.. University Lille Nord; Francia. Inserm; Francia
Fil: Bucci, M.. University Lille Nord; Francia
Fil: Geffroy, S.. University Lille Nord; Francia. Inserm; Francia
Fil: Micol, J.-B.. Université de Paris XI; Francia. Inserm; Francia. Weill Cornell Medical College; Estados Unidos
Fil: Renneville, A.. University Lille Nord; Francia. Inserm; Francia
Fil: Boissel, N.. Université Paris Diderot - Paris 7; Francia
Fil: Dhédin, N.. Université Paris Diderot - Paris 7; Francia
Fil: Réa, D.. Université Paris Diderot - Paris 7; Francia
Fil: Nelken, B.. CHU of Lille. Department of Pediatric Hematology; Francia
Fil: Berthon, C.. Inserm; Francia. CHU of Lille. Department of Pediatric Hematology; Francia
Fil: Leblanc, T.. Hôpital Robert Debré; Francia
Fil: Mozziconacci, M. J.. Institut Paoli-Calmettes; Francia
Fil: Favier, R.. Inserm; Francia. Hôpital Trousseau; Francia. Université de Paris XI; Francia
Fil: Heller, Paula Graciela. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina. 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: Abdel Wahab, O.. Weill Cornell Medical College; Estados Unidos. Memorial Sloan-Kettering Cancer Center; Estados Unidos
Fil: Raslova, H.. Inserm; Francia. Université de Paris XI; Francia
Fil: Latger Cannard, V.. Nancy University Hospital; Francia
Fil: Preudhomme, C.. Inserm; Francia. University Lille Nord; Francia
description The familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML) represents a unique model to study leukemic progression. Whereas qualitative or quantitative platelet defects are a constant feature of the disease, the onset of the hematological malignancy can be very heterogeneous and the molecular mechanisms responsible for leukemia progression remain poorly understood. We analyzed a cohort of 25 individuals from 15 FPD/AML pedigrees for mutations in 44 AML-associated genes, including genes recently associated with germline or acquired RUNX1 aberrations such as CDC25C, GATA2 and ASXL1/2. Of the 25 patients, 13 were studied following acute leukemia development (10 with acute myeloid leukemia (AML) and 3 with T-cell acute lymphoblastic leukemia). Interestingly, a second, somatically acquired alteration in RUNX1 was found in nearly all patients who developed AML, including second mutation, copy neutral loss of heterozygosity or duplication of the RUNX1-mutated or -deleted allele. These latter two events were identified by analysis of the allelic ratio coupled with karyotype. Additional somatic mutations in genes implicated in signaling, RNA splicing or epigenetic regulation were also identified at leukemic transformation. Our findings suggest that biallelic RUNX1 alterations are crucial for AML development in FPD/AML.
publishDate 2016
dc.date.none.fl_str_mv 2016-04
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/11336/39326
Antony Debré, I.; Duployez, N.; Bucci, M.; Geffroy, S.; Micol, J.-B.; et al.; Somatic mutations associated with leukemic progression of familial platelet disorder with predisposition to acute myeloid leukemia; Nature Publishing Group; Leukemia; 30; 4; 4-2016; 999-1002
0887-6924
CONICET Digital
CONICET
url http://hdl.handle.net/11336/39326
identifier_str_mv Antony Debré, I.; Duployez, N.; Bucci, M.; Geffroy, S.; Micol, J.-B.; et al.; Somatic mutations associated with leukemic progression of familial platelet disorder with predisposition to acute myeloid leukemia; Nature Publishing Group; Leukemia; 30; 4; 4-2016; 999-1002
0887-6924
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/leu2015236
info:eu-repo/semantics/altIdentifier/doi/10.1038/leu.2015.236
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
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
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 13.13397

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