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| Home > Articles > Published articles > Development Refractoriness of MLL-Rearranged Human B Cell Acute Leukemias to Reprogramming into Pluripotency |
| Home > Articles > Published articles > Development Refractoriness of MLL-Rearranged Human B Cell Acute Leukemias to Reprogramming into Pluripotency |
(Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras) (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras) (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras) (Instituto de Biomedicina y Biotecnología de Cantabria) (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras) (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras) (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras) (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol) (Hospital Clínico Universitario Virgen de la Arrixaca (El Palmar, Múrcia)) (Instituto Universitario de Oncología del Principado de Asturias (Oviedo)) (Università degli Studi di Milano-Bicocca) (Università degli Studi di Milano-Bicocca) (Instituto Universitario de Oncología del Principado de Asturias (Oviedo)) (Instituto Universitario de Oncología del Principado de Asturias (Oviedo)) (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras) (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
| Date: | 2016 |
| 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. |
| Grants: | European Commission 646903 Instituto de Salud Carlos III FEDER/E-Rare-2CallPI12/03112 Instituto de Salud Carlos III FEDER/E-Rare-2CallPI14/01191 Ministerio de Economía y Competitividad SAF2013-43065 Ministerio de Economía y Competitividad CPII13/00011 Ministerio de Economía y Competitividad BES-2014-067844 |
| Note: | Altres ajuts: Asociación Española Contra el Cáncer, Obra Social La Caixa i Fundació Josep Carreras |
| Note: | Altres ajuts: FI11/0511 |
| Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Subject: | Leucèmia aguda ; Cèl·lules pluripotents induïdes ; B-ALL ; DNA methylome ; MLL-AF4 ; Sendai virus ; Cancer reprogramming ; Ipsc ; Transcriptome ; Pluripotent stem cell ; Acute leukemia |
| Published in: | Stem cell reports, Vol. 7 Núm. 4 (October 2016) , ISSN 2213-6711 |
