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Title: | Developmental refractoriness of MLL-rearranged human B-cell acute leukemias to reprogramming into pluripotency |
Author: | Muñoz, Alvaro Romero Moya, Damià Prieto, Cristina Ramos-Mejía, Verónica Agraz-Doblas, Antonio Varela, Ignacio Buschbeck, Marcus Palau de Miguel, Anna Carvajal-Vergara, Xonia Giorgetti, Alessandra Ford, Anthony Lako, Majlinda Granada, Isabel Ruiz-Xivillé, Neus Rodríguez-Perales, Sandra Torres-Ruíz, Raul Stam, Ronald W. Fuster, Jose Luis Fraga, Mario F. Nakanishi, Mahito Cazzaniga, Gianni Bardini, Michela Cobo, Isabel Bayón, Gustavo F. Fernández, Agustín F. Bueno, Clara Menéndez Buján, Pablo |
Keywords: | Leucèmia Cèl·lules Genètica Leukemia Cells Genetics |
Issue Date: | 11-Oct-2016 |
Publisher: | Elsevier |
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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1016/j.stemcr.2016.08.013 |
It is part of: | Stem Cell Reports, 2016, vol. 7, num. 4, p. 602-618 |
URI: | http://hdl.handle.net/2445/176471 |
Related resource: | https://doi.org/10.1016/j.stemcr.2016.08.013 |
ISSN: | 2213-6711 |
Appears in Collections: | Articles publicats en revistes (Patologia i Terapèutica Experimental) Articles publicats en revistes (Biomedicina) |
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