Germline mutations in ETV6 are associated with thrombocytopenia, red cell macrocytosis and predisposition to lymphoblastic leukemia
- Autores
- Noetzli, Leila; Lo, Richard W.; Lee Sherick, Alisa B.; Callaghan, Michael; Noris, Patrizia; Savoia, Anna; Rajpurkar, Madhvi; Jones, Kenneth; Gowan, Katherine; Balduini, Carlo L; Pecci, Alessandro; Gnan, Chiara; De Rocco, Daniela; Doubek, Michael; Li, Ling; Lu, Lily; Leung, Richard; Landolt Marticorena, Carolina; Hunger, Stephen; Heller, Paula Graciela; Gutierrez Hartmann, Arthur; Xiayuan, Liang; Pluthero, Fred G.; Rowley, Jesse W.; Weyrich, Andrew S.; Kahr, Walter H. A.; Porter, Christopher C.; Di Paola, Jorge
- Año de publicación
- 2015
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Some familial platelet disorders are associated with predisposition to leukemia, myelodysplastic syndrome (MDS) or dyserythropoietic anemia. We identified a family with autosomal dominant thrombocytopenia, high erythrocyte mean corpuscular volume (MCV) and two occurrences of B cell-precursor acute lymphoblastic leukemia (ALL). Whole-exome sequencing identified a heterozygous single-nucleotide change in ETV6 (ets variant 6), c.641C>T, encoding a p.Pro214Leu substitution in the central domain, segregating with thrombocytopenia and elevated MCV. A screen of 23 families with similar phenotypes identified 2 with ETV6 mutations. One family also had a mutation encoding p.Pro214Leu and one individual with ALL. The other family had a c.1252A>G transition producing a p.Arg418Gly substitution in the DNA-binding domain, with alternative splicing and exon skipping. Functional characterization of these mutations showed aberrant cellular localization of mutant and endogenous ETV6, decreased transcriptional repression and altered megakaryocyte maturation. Our findings underscore a key role for ETV6 in platelet formation and leukemia predisposition.
Fil: Noetzli, Leila. University of Colorado. Anschutz Medical Campus; Estados Unidos
Fil: Lo, Richard W.. University of Toronto; Canadá. Hospital for Sick Children. Research Institute; Canadá
Fil: Lee Sherick, Alisa B.. University of Colorado. Anschutz Medical Campus; Estados Unidos
Fil: Callaghan, Michael. Wayne State University; Estados Unidos
Fil: Noris, Patrizia. Università degli Studi di Pavia; Italia
Fil: Savoia, Anna. Istituto di Ricovero e Cura a Carattere Scientifico Burlo Garofolo. Institute for Maternal and Child Health; Italia. Università degli Studi di Trieste; Italia
Fil: Rajpurkar, Madhvi. Wayne State University; Estados Unidos
Fil: Jones, Kenneth. University of Colorado. Anschutz Medical Campus; Estados Unidos
Fil: Gowan, Katherine. University of Colorado. Anschutz Medical Campus; Estados Unidos
Fil: Balduini, Carlo L. Università degli Studi di Pavia; Italia
Fil: Pecci, Alessandro. Università degli Studi di Pavia; Italia
Fil: Gnan, Chiara. Istituto di Ricovero e Cura a Carattere Scientifico Burlo Garofolo. Institute for Maternal and Child Health; Italia. Università degli Studi di Trieste; Italia
Fil: De Rocco, Daniela. Università degli Studi di Trieste; Italia. Istituto di Ricovero e Cura a Carattere Scientifico Burlo Garofolo. Institute for Maternal and Child Health; Italia
Fil: Doubek, Michael. University Hospital Brno; República Checa
Fil: Li, Ling. Hospital for Sick Children. Research Institute; Canadá
Fil: Lu, Lily. Hospital for Sick Children. Research Institute; Canadá
Fil: Leung, Richard. Hospital for Sick Children. Research Institute; Canadá
Fil: Landolt Marticorena, Carolina. University of Toronto; Canadá
Fil: Hunger, Stephen. University of Colorado. Anschutz Medical Campus; Estados Unidos
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
Fil: Gutierrez Hartmann, Arthur. University of Colorado. Anschutz Medical Campus; Estados Unidos
Fil: Xiayuan, Liang. University of Colorado. Anschutz Medical Campus; Estados Unidos
Fil: Pluthero, Fred G.. Hospital for Sick Children. Research Institute; Canadá
Fil: Rowley, Jesse W.. University of Utah; Estados Unidos
Fil: Weyrich, Andrew S.. University of Utah; Estados Unidos
Fil: Kahr, Walter H. A.. Hospital for Sick Children. Research Institute; Canadá. University of Toronto; Canadá
Fil: Porter, Christopher C.. University of Colorado. Anschutz Medical Campus; Estados Unidos
Fil: Di Paola, Jorge. University of Colorado. Anschutz Medical Campus; Estados Unidos - Materia
-
Etv6
Thrombocytopenia
Leukemia - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/45194
Ver los metadatos del registro completo
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Germline mutations in ETV6 are associated with thrombocytopenia, red cell macrocytosis and predisposition to lymphoblastic leukemiaNoetzli, LeilaLo, Richard W.Lee Sherick, Alisa B.Callaghan, MichaelNoris, PatriziaSavoia, AnnaRajpurkar, MadhviJones, KennethGowan, KatherineBalduini, Carlo LPecci, AlessandroGnan, ChiaraDe Rocco, DanielaDoubek, MichaelLi, LingLu, LilyLeung, RichardLandolt Marticorena, CarolinaHunger, StephenHeller, Paula GracielaGutierrez Hartmann, ArthurXiayuan, LiangPluthero, Fred G.Rowley, Jesse W.Weyrich, Andrew S.Kahr, Walter H. A.Porter, Christopher C.Di Paola, JorgeEtv6ThrombocytopeniaLeukemiahttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Some familial platelet disorders are associated with predisposition to leukemia, myelodysplastic syndrome (MDS) or dyserythropoietic anemia. We identified a family with autosomal dominant thrombocytopenia, high erythrocyte mean corpuscular volume (MCV) and two occurrences of B cell-precursor acute lymphoblastic leukemia (ALL). Whole-exome sequencing identified a heterozygous single-nucleotide change in ETV6 (ets variant 6), c.641C>T, encoding a p.Pro214Leu substitution in the central domain, segregating with thrombocytopenia and elevated MCV. A screen of 23 families with similar phenotypes identified 2 with ETV6 mutations. One family also had a mutation encoding p.Pro214Leu and one individual with ALL. The other family had a c.1252A>G transition producing a p.Arg418Gly substitution in the DNA-binding domain, with alternative splicing and exon skipping. Functional characterization of these mutations showed aberrant cellular localization of mutant and endogenous ETV6, decreased transcriptional repression and altered megakaryocyte maturation. Our findings underscore a key role for ETV6 in platelet formation and leukemia predisposition.Fil: Noetzli, Leila. University of Colorado. Anschutz Medical Campus; Estados UnidosFil: Lo, Richard W.. University of Toronto; Canadá. Hospital for Sick Children. Research Institute; CanadáFil: Lee Sherick, Alisa B.. University of Colorado. Anschutz Medical Campus; Estados UnidosFil: Callaghan, Michael. Wayne State University; Estados UnidosFil: Noris, Patrizia. Università degli Studi di Pavia; ItaliaFil: Savoia, Anna. Istituto di Ricovero e Cura a Carattere Scientifico Burlo Garofolo. Institute for Maternal and Child Health; Italia. Università degli Studi di Trieste; ItaliaFil: Rajpurkar, Madhvi. Wayne State University; Estados UnidosFil: Jones, Kenneth. University of Colorado. Anschutz Medical Campus; Estados UnidosFil: Gowan, Katherine. University of Colorado. Anschutz Medical Campus; Estados UnidosFil: Balduini, Carlo L. Università degli Studi di Pavia; ItaliaFil: Pecci, Alessandro. Università degli Studi di Pavia; ItaliaFil: Gnan, Chiara. Istituto di Ricovero e Cura a Carattere Scientifico Burlo Garofolo. Institute for Maternal and Child Health; Italia. Università degli Studi di Trieste; ItaliaFil: De Rocco, Daniela. Università degli Studi di Trieste; Italia. Istituto di Ricovero e Cura a Carattere Scientifico Burlo Garofolo. Institute for Maternal and Child Health; ItaliaFil: Doubek, Michael. University Hospital Brno; República ChecaFil: Li, Ling. Hospital for Sick Children. Research Institute; CanadáFil: Lu, Lily. Hospital for Sick Children. Research Institute; CanadáFil: Leung, Richard. Hospital for Sick Children. Research Institute; CanadáFil: Landolt Marticorena, Carolina. University of Toronto; CanadáFil: Hunger, Stephen. University of Colorado. Anschutz Medical Campus; Estados UnidosFil: 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; ArgentinaFil: Gutierrez Hartmann, Arthur. University of Colorado. Anschutz Medical Campus; Estados UnidosFil: Xiayuan, Liang. University of Colorado. Anschutz Medical Campus; Estados UnidosFil: Pluthero, Fred G.. Hospital for Sick Children. Research Institute; CanadáFil: Rowley, Jesse W.. University of Utah; Estados UnidosFil: Weyrich, Andrew S.. University of Utah; Estados UnidosFil: Kahr, Walter H. A.. Hospital for Sick Children. Research Institute; Canadá. University of Toronto; CanadáFil: Porter, Christopher C.. University of Colorado. Anschutz Medical Campus; Estados UnidosFil: Di Paola, Jorge. University of Colorado. Anschutz Medical Campus; Estados UnidosNature Publishing Group2015-03-25info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/45194Noetzli, Leila; Lo, Richard W.; Lee Sherick, Alisa B.; Callaghan, Michael; Noris, Patrizia; et al.; Germline mutations in ETV6 are associated with thrombocytopenia, red cell macrocytosis and predisposition to lymphoblastic leukemia; Nature Publishing Group; Nature Genetics; 47; 5; 25-3-2015; 535-5381061-40361546-1718CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/ng.3253info:eu-repo/semantics/altIdentifier/doi/10.1038/ng.3253info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-17T11:25:20Zoai:ri.conicet.gov.ar:11336/45194instacron: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:34982025-09-17 11:25:21.269CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| dc.title.none.fl_str_mv |
Germline mutations in ETV6 are associated with thrombocytopenia, red cell macrocytosis and predisposition to lymphoblastic leukemia |
| title |
Germline mutations in ETV6 are associated with thrombocytopenia, red cell macrocytosis and predisposition to lymphoblastic leukemia |
| spellingShingle |
Germline mutations in ETV6 are associated with thrombocytopenia, red cell macrocytosis and predisposition to lymphoblastic leukemia Noetzli, Leila Etv6 Thrombocytopenia Leukemia |
| title_short |
Germline mutations in ETV6 are associated with thrombocytopenia, red cell macrocytosis and predisposition to lymphoblastic leukemia |
| title_full |
Germline mutations in ETV6 are associated with thrombocytopenia, red cell macrocytosis and predisposition to lymphoblastic leukemia |
| title_fullStr |
Germline mutations in ETV6 are associated with thrombocytopenia, red cell macrocytosis and predisposition to lymphoblastic leukemia |
| title_full_unstemmed |
Germline mutations in ETV6 are associated with thrombocytopenia, red cell macrocytosis and predisposition to lymphoblastic leukemia |
| title_sort |
Germline mutations in ETV6 are associated with thrombocytopenia, red cell macrocytosis and predisposition to lymphoblastic leukemia |
| dc.creator.none.fl_str_mv |
Noetzli, Leila Lo, Richard W. Lee Sherick, Alisa B. Callaghan, Michael Noris, Patrizia Savoia, Anna Rajpurkar, Madhvi Jones, Kenneth Gowan, Katherine Balduini, Carlo L Pecci, Alessandro Gnan, Chiara De Rocco, Daniela Doubek, Michael Li, Ling Lu, Lily Leung, Richard Landolt Marticorena, Carolina Hunger, Stephen Heller, Paula Graciela Gutierrez Hartmann, Arthur Xiayuan, Liang Pluthero, Fred G. Rowley, Jesse W. Weyrich, Andrew S. Kahr, Walter H. A. Porter, Christopher C. Di Paola, Jorge |
| author |
Noetzli, Leila |
| author_facet |
Noetzli, Leila Lo, Richard W. Lee Sherick, Alisa B. Callaghan, Michael Noris, Patrizia Savoia, Anna Rajpurkar, Madhvi Jones, Kenneth Gowan, Katherine Balduini, Carlo L Pecci, Alessandro Gnan, Chiara De Rocco, Daniela Doubek, Michael Li, Ling Lu, Lily Leung, Richard Landolt Marticorena, Carolina Hunger, Stephen Heller, Paula Graciela Gutierrez Hartmann, Arthur Xiayuan, Liang Pluthero, Fred G. Rowley, Jesse W. Weyrich, Andrew S. Kahr, Walter H. A. Porter, Christopher C. Di Paola, Jorge |
| author_role |
author |
| author2 |
Lo, Richard W. Lee Sherick, Alisa B. Callaghan, Michael Noris, Patrizia Savoia, Anna Rajpurkar, Madhvi Jones, Kenneth Gowan, Katherine Balduini, Carlo L Pecci, Alessandro Gnan, Chiara De Rocco, Daniela Doubek, Michael Li, Ling Lu, Lily Leung, Richard Landolt Marticorena, Carolina Hunger, Stephen Heller, Paula Graciela Gutierrez Hartmann, Arthur Xiayuan, Liang Pluthero, Fred G. Rowley, Jesse W. Weyrich, Andrew S. Kahr, Walter H. A. Porter, Christopher C. Di Paola, Jorge |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Etv6 Thrombocytopenia Leukemia |
| topic |
Etv6 Thrombocytopenia Leukemia |
| purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.2 https://purl.org/becyt/ford/3 |
| dc.description.none.fl_txt_mv |
Some familial platelet disorders are associated with predisposition to leukemia, myelodysplastic syndrome (MDS) or dyserythropoietic anemia. We identified a family with autosomal dominant thrombocytopenia, high erythrocyte mean corpuscular volume (MCV) and two occurrences of B cell-precursor acute lymphoblastic leukemia (ALL). Whole-exome sequencing identified a heterozygous single-nucleotide change in ETV6 (ets variant 6), c.641C>T, encoding a p.Pro214Leu substitution in the central domain, segregating with thrombocytopenia and elevated MCV. A screen of 23 families with similar phenotypes identified 2 with ETV6 mutations. One family also had a mutation encoding p.Pro214Leu and one individual with ALL. The other family had a c.1252A>G transition producing a p.Arg418Gly substitution in the DNA-binding domain, with alternative splicing and exon skipping. Functional characterization of these mutations showed aberrant cellular localization of mutant and endogenous ETV6, decreased transcriptional repression and altered megakaryocyte maturation. Our findings underscore a key role for ETV6 in platelet formation and leukemia predisposition. Fil: Noetzli, Leila. University of Colorado. Anschutz Medical Campus; Estados Unidos Fil: Lo, Richard W.. University of Toronto; Canadá. Hospital for Sick Children. Research Institute; Canadá Fil: Lee Sherick, Alisa B.. University of Colorado. Anschutz Medical Campus; Estados Unidos Fil: Callaghan, Michael. Wayne State University; Estados Unidos Fil: Noris, Patrizia. Università degli Studi di Pavia; Italia Fil: Savoia, Anna. Istituto di Ricovero e Cura a Carattere Scientifico Burlo Garofolo. Institute for Maternal and Child Health; Italia. Università degli Studi di Trieste; Italia Fil: Rajpurkar, Madhvi. Wayne State University; Estados Unidos Fil: Jones, Kenneth. University of Colorado. Anschutz Medical Campus; Estados Unidos Fil: Gowan, Katherine. University of Colorado. Anschutz Medical Campus; Estados Unidos Fil: Balduini, Carlo L. Università degli Studi di Pavia; Italia Fil: Pecci, Alessandro. Università degli Studi di Pavia; Italia Fil: Gnan, Chiara. Istituto di Ricovero e Cura a Carattere Scientifico Burlo Garofolo. Institute for Maternal and Child Health; Italia. Università degli Studi di Trieste; Italia Fil: De Rocco, Daniela. Università degli Studi di Trieste; Italia. Istituto di Ricovero e Cura a Carattere Scientifico Burlo Garofolo. Institute for Maternal and Child Health; Italia Fil: Doubek, Michael. University Hospital Brno; República Checa Fil: Li, Ling. Hospital for Sick Children. Research Institute; Canadá Fil: Lu, Lily. Hospital for Sick Children. Research Institute; Canadá Fil: Leung, Richard. Hospital for Sick Children. Research Institute; Canadá Fil: Landolt Marticorena, Carolina. University of Toronto; Canadá Fil: Hunger, Stephen. University of Colorado. Anschutz Medical Campus; Estados Unidos 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 Fil: Gutierrez Hartmann, Arthur. University of Colorado. Anschutz Medical Campus; Estados Unidos Fil: Xiayuan, Liang. University of Colorado. Anschutz Medical Campus; Estados Unidos Fil: Pluthero, Fred G.. Hospital for Sick Children. Research Institute; Canadá Fil: Rowley, Jesse W.. University of Utah; Estados Unidos Fil: Weyrich, Andrew S.. University of Utah; Estados Unidos Fil: Kahr, Walter H. A.. Hospital for Sick Children. Research Institute; Canadá. University of Toronto; Canadá Fil: Porter, Christopher C.. University of Colorado. Anschutz Medical Campus; Estados Unidos Fil: Di Paola, Jorge. University of Colorado. Anschutz Medical Campus; Estados Unidos |
| description |
Some familial platelet disorders are associated with predisposition to leukemia, myelodysplastic syndrome (MDS) or dyserythropoietic anemia. We identified a family with autosomal dominant thrombocytopenia, high erythrocyte mean corpuscular volume (MCV) and two occurrences of B cell-precursor acute lymphoblastic leukemia (ALL). Whole-exome sequencing identified a heterozygous single-nucleotide change in ETV6 (ets variant 6), c.641C>T, encoding a p.Pro214Leu substitution in the central domain, segregating with thrombocytopenia and elevated MCV. A screen of 23 families with similar phenotypes identified 2 with ETV6 mutations. One family also had a mutation encoding p.Pro214Leu and one individual with ALL. The other family had a c.1252A>G transition producing a p.Arg418Gly substitution in the DNA-binding domain, with alternative splicing and exon skipping. Functional characterization of these mutations showed aberrant cellular localization of mutant and endogenous ETV6, decreased transcriptional repression and altered megakaryocyte maturation. Our findings underscore a key role for ETV6 in platelet formation and leukemia predisposition. |
| publishDate |
2015 |
| dc.date.none.fl_str_mv |
2015-03-25 |
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info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
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article |
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publishedVersion |
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http://hdl.handle.net/11336/45194 Noetzli, Leila; Lo, Richard W.; Lee Sherick, Alisa B.; Callaghan, Michael; Noris, Patrizia; et al.; Germline mutations in ETV6 are associated with thrombocytopenia, red cell macrocytosis and predisposition to lymphoblastic leukemia; Nature Publishing Group; Nature Genetics; 47; 5; 25-3-2015; 535-538 1061-4036 1546-1718 CONICET Digital CONICET |
| url |
http://hdl.handle.net/11336/45194 |
| identifier_str_mv |
Noetzli, Leila; Lo, Richard W.; Lee Sherick, Alisa B.; Callaghan, Michael; Noris, Patrizia; et al.; Germline mutations in ETV6 are associated with thrombocytopenia, red cell macrocytosis and predisposition to lymphoblastic leukemia; Nature Publishing Group; Nature Genetics; 47; 5; 25-3-2015; 535-538 1061-4036 1546-1718 CONICET Digital CONICET |
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eng |
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eng |
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Nature Publishing Group |
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