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oai:repisalud.isciii.es:20.500.12105/85342025-04-29T10:19:37Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Muñoz-López, Alvaro author Romero-Moya, Damià author Prieto, Cristina author Ramos-Mejía, Verónica author Agraz-Doblas, Antonio author Varela, Ignacio author Buschbeck, Marcus author Palau, Anna author Carvajal-Vergara, Xonia author Giorgetti, Alessandra author Ford, Anthony author Lako, Majlinda author Granada, Isabel author Ruiz-Xivillé, Neus author Rodriguez Perales, Sandra author Torres-Ruiz Raul, Raul author Stam, Ronald W author Fuster, Jose Luis author Fraga, Mario F author Nakanishi, Mahito author Cazzaniga, Gianni author Bardini, Michela author Cobo, Isabel author Bayon, Gustavo F author Fernandez, Agustín F author Bueno, Clara author Menéndez, Pablo author 2016-10-11 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. Stem Cell Reports. 2016;7(4):602-618. 10.1016/j.stemcr.2016.08.013 2213-6711 22136711 Stem cell reports 27666791 http://hdl.handle.net/20.500.12105/8534 B-ALL DNA methylome MLL-AF4 Sendai virus Cancer reprogramming iPSC Transcriptome Development Refractoriness of MLL-Rearranged Human B Cell Acute Leukemias to Reprogramming into Pluripotency