RT Journal Article
T1 Development Refractoriness of MLL-Rearranged Human B Cell Acute Leukemias to Reprogramming into Pluripotency.
A1 Muñoz-López, Alvaro
A1 Romero-Moya, Damià
A1 Prieto, Cristina
A1 Ramos-Mejía, Verónica
A1 Agraz-Doblas, Antonio
A1 Varela, Ignacio
A1 Buschbeck, Marcus
A1 Palau, Anna
A1 Carvajal-Vergara, Xonia
A1 Giorgetti, Alessandra
A1 Ford, Anthony
A1 Lako, Majlinda
A1 Granada, Isabel
A1 Ruiz-Xivillé, Neus
A1 Rodríguez-Perales, Sandra
A1 Torres-Ruíz, Raul
A1 Stam, Ronald W
A1 Fuster, Jose Luis
A1 Fraga, Mario F
A1 Nakanishi, Mahito
A1 Cazzaniga, Gianni
A1 Bardini, Michela
A1 Cobo, Isabel
A1 Bayon, Gustavo F
A1 Fernandez, Agustin F
A1 Bueno, Clara
A1 Menendez, Pablo
K1 B-ALL
K1 DNA methylome
K1 MLL-AF4
K1 Sendai virus
K1 cancer reprogramming
K1 iPSC
K1 transcriptome
AB 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.
YR 2016
FD 2016-09-22
LK http://hdl.handle.net/10668/10474
UL http://hdl.handle.net/10668/10474
LA en
DS RISalud
RD Apr 5, 2025