MLL-rearranged B lymphoblastic leukemias selectively express the immunoregulatory carbohydrate-binding protein galectin-1

Autores
Juszczynski, Przemyslaw; Rodig, Scott J.; Ouyang, Jing; O´Donnell, Evan; Takeyama, Kunihiko; Mlynarski, Wojciech; Mycko, Katarzyna; Szczepanski, Tomasz; Gaworczyk, Anna; Krivtsov, Andrei; Faber, Joerg; Sinha, Amit U.; Rabinovich, Gabriel Adrián; Armstrong, Scott A.; Kutok, Jeffery; Shipp, Margaret A.
Año de publicación
2010
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Leukemias with 11q23 translocations involving the Mixed Lineage Leukemia (MLL) gene exhibit unique clinical and biological features and have a poor prognosis. In a screen for molecular markers of MLL rearrangement, we identified the specific overexpression of an immunomodulatory lectin Galectin-1 (Gal1) in MLL-rearranged B lymphoblastic leukemias (B-ALL) compared to other MLL-germline ALLs. To assess the diagnostic utility of Gal1 expression in identifying MLL-rearranged B-ALLs, we performed Gal1 immunostaining on a large series of primary ALLs with known MLL status. All 11 MLL-rearranged B-ALLs had abundant Gal1 expression; in marked contrast, only 1 of 42 germline-MLL B-ALLs expressed Gal1. In addition, Gal1 was readily detected in diagnostic samples of MLL-rearranged B-ALLs by intracellular flow cytometry. Since deregulated gene expression in MLL-rearranged leukemias may be related to the altered histone methyltransferase activity of MLL fusion protein complex, we analyzed histone H3 lysine 79 (H3K79) dimethylation in the Gal1 promoter region using chromatin immunoprecipitation. Gal1 promoter H3K79diMe was ≈ 5 fold higher in a MLL-rearranged B-ALL cell line than in a B-ALL line without the MLL translocation. Furthermore, the Gal1 promoter H3K79 was significantly hypermethylated in primary MLL-rearranged B-ALLs compared to MLL-germline B-ALLs and normal pre-B cells, implicating this epigenetic modification as a mechanism for Gal1 overexpression in MLL B-ALL.
Fil: Juszczynski, Przemyslaw. Dana Farber Cancer Institute; Estados Unidos
Fil: Rodig, Scott J.. Brigham & Women; Estados Unidos
Fil: Ouyang, Jing. Dana Farber Cancer Institute; Estados Unidos
Fil: O´Donnell, Evan. Dana Farber Cancer Institute; Estados Unidos
Fil: Takeyama, Kunihiko. Dana Farber Cancer Institute; Estados Unidos
Fil: Mlynarski, Wojciech. Dana Farber Cancer Institute; Estados Unidos
Fil: Mycko, Katarzyna. Dana Farber Cancer Institute; Estados Unidos
Fil: Szczepanski, Tomasz. Dana Farber Cancer Institute; Estados Unidos
Fil: Gaworczyk, Anna. Medical University of Lodz; Polonia
Fil: Krivtsov, Andrei. Medical University of Lodz; Polonia
Fil: Faber, Joerg. Medical University of Silesia; Polonia
Fil: Sinha, Amit U.. Medical University of Lublin; Polonia
Fil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina
Fil: Armstrong, Scott A.. Children; Estados Unidos
Fil: Kutok, Jeffery. Children; Estados Unidos
Fil: Shipp, Margaret A.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina
Materia
Mll
B Cell Leukemia
Glycans
Galectin-1
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:11336/14676
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/14676
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling MLL-rearranged B lymphoblastic leukemias selectively express the immunoregulatory carbohydrate-binding protein galectin-1Juszczynski, PrzemyslawRodig, Scott J.Ouyang, JingO´Donnell, EvanTakeyama, KunihikoMlynarski, WojciechMycko, KatarzynaSzczepanski, TomaszGaworczyk, AnnaKrivtsov, AndreiFaber, JoergSinha, Amit U.Rabinovich, Gabriel AdriánArmstrong, Scott A.Kutok, JefferyShipp, Margaret A.MllB Cell LeukemiaGlycansGalectin-1https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Leukemias with 11q23 translocations involving the Mixed Lineage Leukemia (MLL) gene exhibit unique clinical and biological features and have a poor prognosis. In a screen for molecular markers of MLL rearrangement, we identified the specific overexpression of an immunomodulatory lectin Galectin-1 (Gal1) in MLL-rearranged B lymphoblastic leukemias (B-ALL) compared to other MLL-germline ALLs. To assess the diagnostic utility of Gal1 expression in identifying MLL-rearranged B-ALLs, we performed Gal1 immunostaining on a large series of primary ALLs with known MLL status. All 11 MLL-rearranged B-ALLs had abundant Gal1 expression; in marked contrast, only 1 of 42 germline-MLL B-ALLs expressed Gal1. In addition, Gal1 was readily detected in diagnostic samples of MLL-rearranged B-ALLs by intracellular flow cytometry. Since deregulated gene expression in MLL-rearranged leukemias may be related to the altered histone methyltransferase activity of MLL fusion protein complex, we analyzed histone H3 lysine 79 (H3K79) dimethylation in the Gal1 promoter region using chromatin immunoprecipitation. Gal1 promoter H3K79diMe was ≈ 5 fold higher in a MLL-rearranged B-ALL cell line than in a B-ALL line without the MLL translocation. Furthermore, the Gal1 promoter H3K79 was significantly hypermethylated in primary MLL-rearranged B-ALLs compared to MLL-germline B-ALLs and normal pre-B cells, implicating this epigenetic modification as a mechanism for Gal1 overexpression in MLL B-ALL.Fil: Juszczynski, Przemyslaw. Dana Farber Cancer Institute; Estados UnidosFil: Rodig, Scott J.. Brigham & Women; Estados UnidosFil: Ouyang, Jing. Dana Farber Cancer Institute; Estados UnidosFil: O´Donnell, Evan. Dana Farber Cancer Institute; Estados UnidosFil: Takeyama, Kunihiko. Dana Farber Cancer Institute; Estados UnidosFil: Mlynarski, Wojciech. Dana Farber Cancer Institute; Estados UnidosFil: Mycko, Katarzyna. Dana Farber Cancer Institute; Estados UnidosFil: Szczepanski, Tomasz. Dana Farber Cancer Institute; Estados UnidosFil: Gaworczyk, Anna. Medical University of Lodz; PoloniaFil: Krivtsov, Andrei. Medical University of Lodz; PoloniaFil: Faber, Joerg. Medical University of Silesia; PoloniaFil: Sinha, Amit U.. Medical University of Lublin; PoloniaFil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; ArgentinaFil: Armstrong, Scott A.. Children; Estados UnidosFil: Kutok, Jeffery. Children; Estados UnidosFil: Shipp, Margaret A.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; ArgentinaAmerican Association for Cancer Research2010-04-01info: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/11336/14676Juszczynski, Przemyslaw; Rodig, Scott J.; Ouyang, Jing; O´Donnell, Evan; Takeyama, Kunihiko; et al.; MLL-rearranged B lymphoblastic leukemias selectively express the immunoregulatory carbohydrate-binding protein galectin-1; American Association for Cancer Research; Clinical Cancer Research; 16; 7; 1-4-2010; 2122-21301078-04321557-3265enginfo:eu-repo/semantics/altIdentifier/url/http://clincancerres.aacrjournals.org/content/16/7/2122.figures-onlyinfo:eu-repo/semantics/altIdentifier/doi/10.1158/1078-0432.CCR-09-2765info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2920144/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:55:59Zoai:ri.conicet.gov.ar:11336/14676instacron: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 09:55:59.437CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv MLL-rearranged B lymphoblastic leukemias selectively express the immunoregulatory carbohydrate-binding protein galectin-1
title MLL-rearranged B lymphoblastic leukemias selectively express the immunoregulatory carbohydrate-binding protein galectin-1
spellingShingle MLL-rearranged B lymphoblastic leukemias selectively express the immunoregulatory carbohydrate-binding protein galectin-1
Juszczynski, Przemyslaw
Mll
B Cell Leukemia
Glycans
Galectin-1
title_short MLL-rearranged B lymphoblastic leukemias selectively express the immunoregulatory carbohydrate-binding protein galectin-1
title_full MLL-rearranged B lymphoblastic leukemias selectively express the immunoregulatory carbohydrate-binding protein galectin-1
title_fullStr MLL-rearranged B lymphoblastic leukemias selectively express the immunoregulatory carbohydrate-binding protein galectin-1
title_full_unstemmed MLL-rearranged B lymphoblastic leukemias selectively express the immunoregulatory carbohydrate-binding protein galectin-1
title_sort MLL-rearranged B lymphoblastic leukemias selectively express the immunoregulatory carbohydrate-binding protein galectin-1
dc.creator.none.fl_str_mv Juszczynski, Przemyslaw
Rodig, Scott J.
Ouyang, Jing
O´Donnell, Evan
Takeyama, Kunihiko
Mlynarski, Wojciech
Mycko, Katarzyna
Szczepanski, Tomasz
Gaworczyk, Anna
Krivtsov, Andrei
Faber, Joerg
Sinha, Amit U.
Rabinovich, Gabriel Adrián
Armstrong, Scott A.
Kutok, Jeffery
Shipp, Margaret A.
author Juszczynski, Przemyslaw
author_facet Juszczynski, Przemyslaw
Rodig, Scott J.
Ouyang, Jing
O´Donnell, Evan
Takeyama, Kunihiko
Mlynarski, Wojciech
Mycko, Katarzyna
Szczepanski, Tomasz
Gaworczyk, Anna
Krivtsov, Andrei
Faber, Joerg
Sinha, Amit U.
Rabinovich, Gabriel Adrián
Armstrong, Scott A.
Kutok, Jeffery
Shipp, Margaret A.
author_role author
author2 Rodig, Scott J.
Ouyang, Jing
O´Donnell, Evan
Takeyama, Kunihiko
Mlynarski, Wojciech
Mycko, Katarzyna
Szczepanski, Tomasz
Gaworczyk, Anna
Krivtsov, Andrei
Faber, Joerg
Sinha, Amit U.
Rabinovich, Gabriel Adrián
Armstrong, Scott A.
Kutok, Jeffery
Shipp, Margaret A.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Mll
B Cell Leukemia
Glycans
Galectin-1
topic Mll
B Cell Leukemia
Glycans
Galectin-1
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Leukemias with 11q23 translocations involving the Mixed Lineage Leukemia (MLL) gene exhibit unique clinical and biological features and have a poor prognosis. In a screen for molecular markers of MLL rearrangement, we identified the specific overexpression of an immunomodulatory lectin Galectin-1 (Gal1) in MLL-rearranged B lymphoblastic leukemias (B-ALL) compared to other MLL-germline ALLs. To assess the diagnostic utility of Gal1 expression in identifying MLL-rearranged B-ALLs, we performed Gal1 immunostaining on a large series of primary ALLs with known MLL status. All 11 MLL-rearranged B-ALLs had abundant Gal1 expression; in marked contrast, only 1 of 42 germline-MLL B-ALLs expressed Gal1. In addition, Gal1 was readily detected in diagnostic samples of MLL-rearranged B-ALLs by intracellular flow cytometry. Since deregulated gene expression in MLL-rearranged leukemias may be related to the altered histone methyltransferase activity of MLL fusion protein complex, we analyzed histone H3 lysine 79 (H3K79) dimethylation in the Gal1 promoter region using chromatin immunoprecipitation. Gal1 promoter H3K79diMe was ≈ 5 fold higher in a MLL-rearranged B-ALL cell line than in a B-ALL line without the MLL translocation. Furthermore, the Gal1 promoter H3K79 was significantly hypermethylated in primary MLL-rearranged B-ALLs compared to MLL-germline B-ALLs and normal pre-B cells, implicating this epigenetic modification as a mechanism for Gal1 overexpression in MLL B-ALL.
Fil: Juszczynski, Przemyslaw. Dana Farber Cancer Institute; Estados Unidos
Fil: Rodig, Scott J.. Brigham & Women; Estados Unidos
Fil: Ouyang, Jing. Dana Farber Cancer Institute; Estados Unidos
Fil: O´Donnell, Evan. Dana Farber Cancer Institute; Estados Unidos
Fil: Takeyama, Kunihiko. Dana Farber Cancer Institute; Estados Unidos
Fil: Mlynarski, Wojciech. Dana Farber Cancer Institute; Estados Unidos
Fil: Mycko, Katarzyna. Dana Farber Cancer Institute; Estados Unidos
Fil: Szczepanski, Tomasz. Dana Farber Cancer Institute; Estados Unidos
Fil: Gaworczyk, Anna. Medical University of Lodz; Polonia
Fil: Krivtsov, Andrei. Medical University of Lodz; Polonia
Fil: Faber, Joerg. Medical University of Silesia; Polonia
Fil: Sinha, Amit U.. Medical University of Lublin; Polonia
Fil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina
Fil: Armstrong, Scott A.. Children; Estados Unidos
Fil: Kutok, Jeffery. Children; Estados Unidos
Fil: Shipp, Margaret A.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina
description Leukemias with 11q23 translocations involving the Mixed Lineage Leukemia (MLL) gene exhibit unique clinical and biological features and have a poor prognosis. In a screen for molecular markers of MLL rearrangement, we identified the specific overexpression of an immunomodulatory lectin Galectin-1 (Gal1) in MLL-rearranged B lymphoblastic leukemias (B-ALL) compared to other MLL-germline ALLs. To assess the diagnostic utility of Gal1 expression in identifying MLL-rearranged B-ALLs, we performed Gal1 immunostaining on a large series of primary ALLs with known MLL status. All 11 MLL-rearranged B-ALLs had abundant Gal1 expression; in marked contrast, only 1 of 42 germline-MLL B-ALLs expressed Gal1. In addition, Gal1 was readily detected in diagnostic samples of MLL-rearranged B-ALLs by intracellular flow cytometry. Since deregulated gene expression in MLL-rearranged leukemias may be related to the altered histone methyltransferase activity of MLL fusion protein complex, we analyzed histone H3 lysine 79 (H3K79) dimethylation in the Gal1 promoter region using chromatin immunoprecipitation. Gal1 promoter H3K79diMe was ≈ 5 fold higher in a MLL-rearranged B-ALL cell line than in a B-ALL line without the MLL translocation. Furthermore, the Gal1 promoter H3K79 was significantly hypermethylated in primary MLL-rearranged B-ALLs compared to MLL-germline B-ALLs and normal pre-B cells, implicating this epigenetic modification as a mechanism for Gal1 overexpression in MLL B-ALL.
publishDate 2010
dc.date.none.fl_str_mv 2010-04-01
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/11336/14676
Juszczynski, Przemyslaw; Rodig, Scott J.; Ouyang, Jing; O´Donnell, Evan; Takeyama, Kunihiko; et al.; MLL-rearranged B lymphoblastic leukemias selectively express the immunoregulatory carbohydrate-binding protein galectin-1; American Association for Cancer Research; Clinical Cancer Research; 16; 7; 1-4-2010; 2122-2130
1078-0432
1557-3265
url http://hdl.handle.net/11336/14676
identifier_str_mv Juszczynski, Przemyslaw; Rodig, Scott J.; Ouyang, Jing; O´Donnell, Evan; Takeyama, Kunihiko; et al.; MLL-rearranged B lymphoblastic leukemias selectively express the immunoregulatory carbohydrate-binding protein galectin-1; American Association for Cancer Research; Clinical Cancer Research; 16; 7; 1-4-2010; 2122-2130
1078-0432
1557-3265
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://clincancerres.aacrjournals.org/content/16/7/2122.figures-only
info:eu-repo/semantics/altIdentifier/doi/10.1158/1078-0432.CCR-09-2765
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2920144/
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 American Association for Cancer Research
publisher.none.fl_str_mv American Association for Cancer Research
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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