COVID-19 concerns aggregate around platelets

Abstract

LSPCs to nonapoptotic, iron-dependent cell death via ferroptosis. Indeed, ferroptosis inhibition functionally rescued Aldh3A2 loss. Conversely, genetic and pharmacologic inhibition of ferroptosis inhibitory glutathione peroxidase 4 (GPX4) and cytotoxic therapy triggered increased elimination of Aldh3a2-deficient LSPCs and extended AML-free survival in vivo compared with aberrant stem cells expressing the detoxifying enzyme. This finding provides further evidence that AML relies on increased metabolic plasticity, particularly enhanced FA metabolism, for desensitizing leukemic clones to cell death 9 ; it also underscores that distinct metabolic adaptations are likely at play in LSPCs and AML blast cells as suggested by Jordan and colleagues. ture studies are needed to continue identifying LSPC-specific metabolic adaptations and vulnerabilities, particularly in the context of therapeutic interventions for AML. It will also be of critical importance to gain insights into the role of metabolic dependencies in pre-LSPCs, as they are not only the cellular source of primary disease initiation, but they provide a pool of highly transformation-susceptible cells during antileukemic therapy. 3,

Topics & Concepts