Lysosomes in acute myeloid leukemia: potential therapeutic targets?

Rafiq, Sreoshee; McKenna, Sharon L; Muller, Sylviane; Tschan, Mario; Humbert, Magali (2021). Lysosomes in acute myeloid leukemia: potential therapeutic targets? Leukemia, 35(10), pp. 2759-2770. Springer Nature 10.1038/s41375-021-01388-x

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Lysosomes, since their discovery, have been primarily known for degrading cellular macromolecules. However, in recent studies, they have begun to emerge as crucial regulators of cell homeostasis. They are at the crossroads of catabolic and anabolic pathways and are intricately involved in cellular trafficking, nutrient signaling, energy metabolism, and immune regulation. Their involvement in such essential cellular functions has renewed clinical interest in targeting the lysosome as a novel way to treat disease, particularly cancer. Acute myeloid leukemia (AML) is an aggressive blood cancer with a low survival probability, particularly in older patients. The genomic landscape of AML has been extensively characterized but few targeted therapies (with the exception of differentiation therapy) can achieve a long-term cure. Therefore, there is an unmet need for less intensive and more tolerable therapeutic interventions. In this review, we will give an overview on the myriad of functions performed by lysosomes and their importance in malignant disease. Furthermore, we will discuss their relevance in hematopoietic cells and different ways to potentially target them in AML.

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