| Autor: |
Nair, Ramya, Salinas-Illarena, Alejandro, Sponheimer, Monika, Wullkopf, Inès, Schreiber, Yannick, Côrte-Real, João Vasco, del Pozo Ben, Augusto, Marterer, Helena, Thomas, Dominique, Geisslinger, Gerd, Cinatl Jr., Jindrich, Subklewe, Marion, Baldauf, Hanna-Mari |
| Předmět: |
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| Zdroj: |
Clinical & Experimental Medicine; 7/13/2024, Vol. 24 Issue 1, p1-14, 14p |
| Abstrakt: |
Knowledge of the molecular pathogenesis of acute myeloid leukemia has advanced in recent years. Despite novel treatment options, acute myeloid leukemia remains a survival challenge for elderly patients. We have recently shown that the triphosphohydrolase SAMHD1 is one of the factors determining resistance to Ara-C treatment. Here, we designed and tested novel and simpler virus-like particles incorporating the lentiviral protein Vpx to efficiently and transiently degrade SAMHD1 and increase the efficacy of Ara-C treatment. The addition of minute amounts of lentiviral Rev protein during production enhanced the generation of virus-like particles. In addition, we found that our 2nd generation of virus-like particles efficiently targeted and degraded SAMHD1 in AML cell lines with high levels of SAMHD1, thereby increasing Ara-CTP levels and response to Ara-C treatment. Primary AML blasts were generally less responsive to VLP treatment. In summary, we have been able to generate novel and simpler virus-like particles that can efficiently deliver Vpx to target cells. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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