Players in Drug-Resistant Leukemia Stem/Initiating Cells and Immunity in Patients with CML in Context of Oxygen Levels: Would Collecting/Processing Cells in Hypoxia Offer Additional Information? A Next Frontier of Investigation.

Chronic myelogenous leukemia (CML) is a stem cell disorder once considered an eventual death sentence upon progression to the terminal acute/blastic cell phase, a terrible clinical outcome that has improved with the introduction of tyrosine kinase inhibitors. A major continuing problem with treating CML is the persistence of drug-resistant leukemia stem/initiating cells (LS/IC). In this issue of Blood Cancer Discovery, Silvestri and colleagues describe an incredibly in-depth mechanistic study using genetic and pharmacologic modulation of the miRNA MiR300 with and without treatment with activators of the serine-threonine protein phosphatase 2A (PP2A) in human cells. In vitro studies and in vivo mouse models of patient-derived xenografts were used to address the need to target LS/ICs and restore immunity of impaired natural killer cells for attenuation of CML progression. See related article by Silvestri et al., p. 48. ©2020 American Association for Cancer Research.