@article{10902/9272,
year = {2016},
url = {http://hdl.handle.net/10902/9272},
abstract = {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.},
publisher = {Cell Press. Elsevier},
publisher = {Stem Cell Reports. 2016 Oct 11;7(4):602-618},
title = {Development Refractoriness of MLL-Rearranged Human B Cell Acute Leukemias to Reprogramming into Pluripotency},
author = {Muñoz López, A and Romero Moya, D and Prieto, C. and Ramos Mejía, V and Agraz Doblas, Antonio Manuel and Varela Egocheaga, Ignacio and Buschbeck, M. and Palau, A and Carvajal Vergara, X and Giorgetti, A and Ford, A and Lako, M and Granada, I and Ruiz Xivillé, N and Rodríguez Perales, S and Torres Ruíz, R and Stam, RW and Fuster, JL and Fraga, MF and Nakanishi, M and Cazzaniga, G and Bardini, M and Cobo, I and Bayon, GF and Fernández Fernández, Agustín and Bueno, C and Menéndez, P},
}