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...

Descripción completa

Detalles Bibliográficos
Autores: 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
Tipo de recurso: artículo
Fecha de publicación:2016
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:174716
Acceso en línea:https://ddd.uab.cat/record/174716
https://dx.doi.org/urn:doi:10.1016/j.stemcr.2016.08.013
Access Level:acceso abierto
Palabra clave:Leucèmia aguda
Cèl·lules pluripotents induïdes
B-ALL
DNA methylome
MLL-AF4
Sendai virus
Cancer reprogramming
Ipsc
Transcriptome
Pluripotent stem cell
Acute leukemia
Descripción
Sumario: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.

Similares en LA Referencia