Diverse temporal and spatial mechanisms work, partially through Stanniocalcin-1, V-ATPase and senescence, to activate the extracellular ATP-mediated drug resistance in human cancer cells.

Introduction: Resistance to drug therapies is associated with a large majority of cancer-related deaths. ATP-binding cassette (ABC) transporter-mediated drug efflux, epithelial-mesenchymal transition (EMT), cancer stem cells (CSCs), glutathione (GSH), senescence, and vacuole-type ATPase (V-ATPase) all contribute to the resistance. We recently showed that extracellular ATP (eATP) induces and regulates EMT, CSC formation, and ABC transporters in human cancer cells and tumors.

Rare germline alterations of myeloperoxidase predispose to myeloid neoplasms.

Myeloperoxidase (MPO) gene alterations with variable clinical penetrance have been found in hereditary MPO deficiency, but their leukemia association in patients and carriers has not been established. Germline MPO alterations were found to be significantly enriched in myeloid neoplasms: 28 pathogenic/likely pathogenic variants were identified in 100 patients. The most common alterations were c.

Cancer stem cells, epithelial-mesenchymal transition, ATP and their roles in drug resistance in cancer.

The cancer stem cell (CSC) state and epithelial-mesenchymal transition (EMT) activation are tightly interconnected. Cancer cells that acquire the EMT/CSC phenotype are equipped with adaptive metabolic changes to maintain low reactive oxygen species levels and stemness, enhanced drug transporters, anti-apoptotic machinery and DNA repair system. Factors present in the tumor microenvironment such as hypoxia and the communication with non-cancer stromal cells also promote cancer cells to enter the EMT/CSC state and display related resistance.