Is there a publication available where an agent has been shown to induce apoptosis in quiescent leukemia stem cells, without inducing entry into cell cycle
Glial fibrillary acidic protein (GFAP). This protein is not expressed on activated cells,
Histone deacetylase inhibitors (HDACi) are a class of agents that have shown promise as a therapy for several cancers (Marks et al., 2004). HDACi can modulate gene expression through increased histone lysine acetylation. Anti-cancer effects may also be related to modulation of the acetylation status of non-histone proteins (Bolden et al., 2006). In contrast to most other pro-apoptotic agents that preferentially target dividing cells, HDACi have been shown to induce apoptosis in non-proliferating cancer cell lines, which may have important implications for elimination of quiescent primitive LSC (Burgess et al., 2004). Treatment with the hydroxamic acid analog pan-HDACi SAHA, LAQ824 (LAQ) or LBH589 (LBH), alone and in combination with TKI has been reported to induce apoptosis in CML cell lines and BC CML cells (Fiskus et al., 2006a; Fiskus et al., 2006b; Nimmanapalli et al., 2003a; Nimmanapalli et al., 2003b). However, BC CML cells may originate from a more mature progenitor population rather than a stem cell, and differ markedly in behavior and therapeutic response from CP CML cells (Calabretta and Perrotti, 2004; Jamieson et al., 2004). The effect of HDACi on primitive LSC from CP CML patients has not been characterized. It is not known whether HDACi are capable of inducing apoptosis in quiescent stem and progenitor cells that resist elimination by BCR-ABL TKI. Here we investigated the effects of the HDACi, LAQ and LBH, alone and in combination with IM, on primitive CML leukemia stem and progenitor cells.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2873971/
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