Development Refractoriness of MLL-Rearranged Human B Cell Acute Leukemias to Reprogramming into Pluripotency
Induced pluripotent stem cells (iPSCs) are a powerful tool for disease modeling. They are routinely generated from healthy donors and patients from multiple cell types at different developmental stages. However, reprogramming leukemias is an extremely inefficient process. Few studies generated iPSCs...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Tipo de documento: | artigo |
| Data de publicação: | 2016 |
| País: | España |
| Recursos: | Universitat Autònoma de Barcelona |
| Repositório: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglês |
| OAI Identifier: | oai:ddd.uab.cat:174716 |
| Acesso em linha: | https://ddd.uab.cat/record/174716 https://dx.doi.org/urn:doi:10.1016/j.stemcr.2016.08.013 |
| Access Level: | Acceso aberto |
| Palavra-chave: | Leucèmia aguda Cèl·lules pluripotents induïdes B-ALL DNA methylome MLL-AF4 Sendai virus Cancer reprogramming Ipsc Transcriptome Pluripotent stem cell Acute leukemia |
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Development Refractoriness of MLL-Rearranged Human B Cell Acute Leukemias to Reprogramming into PluripotencyMuñoz López, Álvaro|||0000-0002-4601-5633Romero Moya, Damià|||0000-0001-9947-3577Prieto, Cristina|||0000-0002-0812-8100Ramos Mejía, VerónicaAgraz-Doblás, Antonio|||0000-0003-1307-4175Varela, Ignacio|||0000-0002-0969-506XBuschbeck, Marcus|||0000-0002-3218-4567Palau de Miguel, Anna|||0000-0003-2131-1265Carvajal Vergara, XoniaGiorgetti, Alessandra|||0000-0001-5803-3567Ford, AnthonyLako, MajlindaGranada, Isabel|||0000-0002-4275-0104Ruiz Xivillé, NeusRodríguez Perales, SandraTorres Ruíz, RaúlStam, Ronald W.Fuster, José Luis|||0000-0002-4881-9440Fraga, Mario|||0000-0001-8450-2603Nakanishi, MahitoCazzaniga, Giovanni|||0000-0003-2955-4528Bardini, Michela|||0000-0002-6942-2274Cobo, IsabelFernández Bayón, Gustavo|||0000-0002-0763-0473Fernández, Agustín F.|||0000-0002-3792-4085Bueno, Clara|||0000-0003-1442-6216Menéndez Bujan, Pablo|||0000-0001-9372-1007Leucèmia agudaCèl·lules pluripotents induïdesB-ALLDNA methylomeMLL-AF4Sendai virusCancer reprogrammingIpscTranscriptomePluripotent stem cellAcute leukemiaInduced pluripotent stem cells (iPSCs) are a powerful tool for disease modeling. They are routinely generated from healthy donors and patients from multiple cell types at different developmental stages. However, reprogramming leukemias is an extremely inefficient process. Few studies generated iPSCs from primary chronic myeloid leukemias, but iPSC generation from acute myeloid or lymphoid leukemias (ALL) has not been achieved. We attempted to generate iPSCs from different subtypes of B-ALL to address the developmental impact of leukemic fusion genes. OKSM(L)-expressing mono/polycistronic-, retroviral/lentiviral/episomal-, and Sendai virus vector-based reprogramming strategies failed to render iPSCs in vitro and in vivo. Addition of transcriptomic-epigenetic reprogramming "boosters" also failed to generate iPSCs from B cell blasts and B-ALL lines, and when iPSCs emerged they lacked leukemic fusion genes, demonstrating non-leukemic myeloid origin. Conversely, MLL-AF4-overexpressing hematopoietic stem cells/B progenitors were successfully reprogrammed, indicating that B cell origin and leukemic fusion gene were not reprogramming barriers. Global transcriptome/DNA methylome profiling suggested a developmental/differentiation refractoriness of MLL-rearranged B-ALL to reprogramming into pluripotency. 22016-01-0120162016-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/174716https://dx.doi.org/urn:doi:10.1016/j.stemcr.2016.08.013reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengEuropean Commission https://doi.org/10.13039/501100000780 646903Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 FEDER/E-Rare-2CallPI12/03112Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 FEDER/E-Rare-2CallPI14/01191Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 SAF2013-43065Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 CPII13/00011Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 BES-2014-067844open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:1747162026-06-06T12:50:31Z |
| dc.title.none.fl_str_mv |
Development Refractoriness of MLL-Rearranged Human B Cell Acute Leukemias to Reprogramming into Pluripotency |
| title |
Development Refractoriness of MLL-Rearranged Human B Cell Acute Leukemias to Reprogramming into Pluripotency |
| spellingShingle |
Development Refractoriness of MLL-Rearranged Human B Cell Acute Leukemias to Reprogramming into Pluripotency Muñoz López, Álvaro|||0000-0002-4601-5633 Leucèmia aguda Cèl·lules pluripotents induïdes B-ALL DNA methylome MLL-AF4 Sendai virus Cancer reprogramming Ipsc Transcriptome Pluripotent stem cell Acute leukemia |
| title_short |
Development Refractoriness of MLL-Rearranged Human B Cell Acute Leukemias to Reprogramming into Pluripotency |
| title_full |
Development Refractoriness of MLL-Rearranged Human B Cell Acute Leukemias to Reprogramming into Pluripotency |
| title_fullStr |
Development Refractoriness of MLL-Rearranged Human B Cell Acute Leukemias to Reprogramming into Pluripotency |
| title_full_unstemmed |
Development Refractoriness of MLL-Rearranged Human B Cell Acute Leukemias to Reprogramming into Pluripotency |
| title_sort |
Development Refractoriness of MLL-Rearranged Human B Cell Acute Leukemias to Reprogramming into Pluripotency |
| dc.creator.none.fl_str_mv |
Muñoz López, Álvaro|||0000-0002-4601-5633 Romero Moya, Damià|||0000-0001-9947-3577 Prieto, Cristina|||0000-0002-0812-8100 Ramos Mejía, Verónica Agraz-Doblás, Antonio|||0000-0003-1307-4175 Varela, Ignacio|||0000-0002-0969-506X Buschbeck, Marcus|||0000-0002-3218-4567 Palau de Miguel, Anna|||0000-0003-2131-1265 Carvajal Vergara, Xonia Giorgetti, Alessandra|||0000-0001-5803-3567 Ford, Anthony Lako, Majlinda Granada, Isabel|||0000-0002-4275-0104 Ruiz Xivillé, Neus Rodríguez Perales, Sandra Torres Ruíz, Raúl Stam, Ronald W. Fuster, José Luis|||0000-0002-4881-9440 Fraga, Mario|||0000-0001-8450-2603 Nakanishi, Mahito Cazzaniga, Giovanni|||0000-0003-2955-4528 Bardini, Michela|||0000-0002-6942-2274 Cobo, Isabel Fernández Bayón, Gustavo|||0000-0002-0763-0473 Fernández, Agustín F.|||0000-0002-3792-4085 Bueno, Clara|||0000-0003-1442-6216 Menéndez Bujan, Pablo|||0000-0001-9372-1007 |
| author |
Muñoz López, Álvaro|||0000-0002-4601-5633 |
| author_facet |
Muñoz López, Álvaro|||0000-0002-4601-5633 Romero Moya, Damià|||0000-0001-9947-3577 Prieto, Cristina|||0000-0002-0812-8100 Ramos Mejía, Verónica Agraz-Doblás, Antonio|||0000-0003-1307-4175 Varela, Ignacio|||0000-0002-0969-506X Buschbeck, Marcus|||0000-0002-3218-4567 Palau de Miguel, Anna|||0000-0003-2131-1265 Carvajal Vergara, Xonia Giorgetti, Alessandra|||0000-0001-5803-3567 Ford, Anthony Lako, Majlinda Granada, Isabel|||0000-0002-4275-0104 Ruiz Xivillé, Neus Rodríguez Perales, Sandra Torres Ruíz, Raúl Stam, Ronald W. Fuster, José Luis|||0000-0002-4881-9440 Fraga, Mario|||0000-0001-8450-2603 Nakanishi, Mahito Cazzaniga, Giovanni|||0000-0003-2955-4528 Bardini, Michela|||0000-0002-6942-2274 Cobo, Isabel Fernández Bayón, Gustavo|||0000-0002-0763-0473 Fernández, Agustín F.|||0000-0002-3792-4085 Bueno, Clara|||0000-0003-1442-6216 Menéndez Bujan, Pablo|||0000-0001-9372-1007 |
| author_role |
author |
| author2 |
Romero Moya, Damià|||0000-0001-9947-3577 Prieto, Cristina|||0000-0002-0812-8100 Ramos Mejía, Verónica Agraz-Doblás, Antonio|||0000-0003-1307-4175 Varela, Ignacio|||0000-0002-0969-506X Buschbeck, Marcus|||0000-0002-3218-4567 Palau de Miguel, Anna|||0000-0003-2131-1265 Carvajal Vergara, Xonia Giorgetti, Alessandra|||0000-0001-5803-3567 Ford, Anthony Lako, Majlinda Granada, Isabel|||0000-0002-4275-0104 Ruiz Xivillé, Neus Rodríguez Perales, Sandra Torres Ruíz, Raúl Stam, Ronald W. Fuster, José Luis|||0000-0002-4881-9440 Fraga, Mario|||0000-0001-8450-2603 Nakanishi, Mahito Cazzaniga, Giovanni|||0000-0003-2955-4528 Bardini, Michela|||0000-0002-6942-2274 Cobo, Isabel Fernández Bayón, Gustavo|||0000-0002-0763-0473 Fernández, Agustín F.|||0000-0002-3792-4085 Bueno, Clara|||0000-0003-1442-6216 Menéndez Bujan, Pablo|||0000-0001-9372-1007 |
| 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 |
| dc.subject.none.fl_str_mv |
Leucèmia aguda Cèl·lules pluripotents induïdes B-ALL DNA methylome MLL-AF4 Sendai virus Cancer reprogramming Ipsc Transcriptome Pluripotent stem cell Acute leukemia |
| topic |
Leucèmia aguda Cèl·lules pluripotents induïdes B-ALL DNA methylome MLL-AF4 Sendai virus Cancer reprogramming Ipsc Transcriptome Pluripotent stem cell Acute leukemia |
| description |
Induced pluripotent stem cells (iPSCs) are a powerful tool for disease modeling. They are routinely generated from healthy donors and patients from multiple cell types at different developmental stages. However, reprogramming leukemias is an extremely inefficient process. Few studies generated iPSCs from primary chronic myeloid leukemias, but iPSC generation from acute myeloid or lymphoid leukemias (ALL) has not been achieved. We attempted to generate iPSCs from different subtypes of B-ALL to address the developmental impact of leukemic fusion genes. OKSM(L)-expressing mono/polycistronic-, retroviral/lentiviral/episomal-, and Sendai virus vector-based reprogramming strategies failed to render iPSCs in vitro and in vivo. Addition of transcriptomic-epigenetic reprogramming "boosters" also failed to generate iPSCs from B cell blasts and B-ALL lines, and when iPSCs emerged they lacked leukemic fusion genes, demonstrating non-leukemic myeloid origin. Conversely, MLL-AF4-overexpressing hematopoietic stem cells/B progenitors were successfully reprogrammed, indicating that B cell origin and leukemic fusion gene were not reprogramming barriers. Global transcriptome/DNA methylome profiling suggested a developmental/differentiation refractoriness of MLL-rearranged B-ALL to reprogramming into pluripotency. |
| publishDate |
2016 |
| dc.date.none.fl_str_mv |
2 2016-01-01 2016 2016-01-01 |
| dc.type.none.fl_str_mv |
Article http://purl.org/coar/resource_type/c_6501 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
https://ddd.uab.cat/record/174716 https://dx.doi.org/urn:doi:10.1016/j.stemcr.2016.08.013 |
| url |
https://ddd.uab.cat/record/174716 https://dx.doi.org/urn:doi:10.1016/j.stemcr.2016.08.013 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.relation.none.fl_str_mv |
European Commission https://doi.org/10.13039/501100000780 646903 Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 FEDER/E-Rare-2CallPI12/03112 Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 FEDER/E-Rare-2CallPI14/01191 Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 SAF2013-43065 Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 CPII13/00011 Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 BES-2014-067844 |
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open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by-nc-nd/4.0/ |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by-nc-nd/4.0/ |
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openAccess |
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application/pdf |
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reponame:Dipòsit Digital de Documents de la UAB instname:Universitat Autònoma de Barcelona |
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