Role of autophagy in acute myeloid leukemia therapy

Abstract

Despite its dual role in determining cell fate in a wide array of solid cancer cell lines, autophagy has been robustly shown to suppress or kill acute myeloid leukemia cells via degradation of the oncogenic fusion protein that drives leukemogenesis. However, autophagy also induces the demise of acute leukemia cells that do not express the known fusion protein, though the molecular mechanism remains elusive. Nevertheless, since it can induce cooperation with apoptosis and differentiation in response to autophagic signals, autophagy can be manipulated for a better therapy on acute myeloid leukemia.

Induction of autophagy is a key component of all-trans-retinoic acid-induced differentiation in leukemia cells and a potential target for pharmacologic modulation

“…As a result, several clinical trials, combining the autophagy inhibitor chloroquine or its sister drug hydroxychloroquine, with conventional chemotherapy are currently underway in both solid and hematologic malignancies [52]. Conversely, studies in hematologic malignancies have shown that several anti-tumor agents promote autophagic cell death, and that this is critical to their efficacy [48, 53]. Our study supports the concept that autophagy induction may be of clinical benefit through promoting terminal differentiation and subsequent cell death.…”

Caspase-3 controls AML1-ETO–driven leukemogenesis via autophagy modulation in a ULK1-dependent manner

“…[31][32][33][34][35] Autophagy was reported to predominantly drive a cytodestructive cascade in human AML that promotes oncogenic fusion protein clearance and leads to cell differentiation and cell death. 36 The autophagy-driven degradation of these fusion oncoproteins (eg, PML-RARA and BCR-ABL) regulates leukemia cell differentiation and cell death, and can contribute to treatment response. 37,38 In human AML, blasts have reduced expression of autophagy-related genes, decreased autophagic flux, and the accumulation of unhealthy mitochondria, indicating that low autophagy activity provides an advantage for the growth of transformed cells.…”

Effect of sintering temperature and time on densification, microstructure and properties of the PZT/ZnO nanowhisker piezoelectric composites

“…In some applications at high power and high stress, their poor mechanical and electrical reliability become a critical limitation [19][20][21][22][23]. In the past few years, a few studies have dealt with improving the mechanical properties of PZT ceramics by incorporating polymers, particles, oxides, metals, fibers or whiskers [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38]. However, the electrical properties of PZT-based composites have been deteriorated greatly.…”