Schematic representation of mechanisms underlying aberrant expansion of aneuploid hematopietic stem cells with −7. During bone marrow failure, hematopietic stem cells are embedded in an inflammatory environment. Although diploid stem cells (green) that accumulate mutations usually are subject to cell-cycle arrest, apoptosis, and effective immune surveillance and eradication, aneuploid stem cells with −7 (red) display downregulation of genes implicated in the regulation of DNA damage checkpoints, cell cycle, and apoptosis, which thereby can facilitate their accumulation of additional mutations and aberrant expansion, ultimately leading to leukemogenesis. AP-1, activator protein 1; DAMP, damage-associated molecular pattern; Fas-L, Fas ligand; IFN-γ, interferon γ; IFNGR, IFN-γ receptor; PAMP, pathogen-associated molecular pattern; TF, transcription factor; TLR, Toll-like receptor; TNF, tumor necrosis factor; TNFR, TNF receptor. The figure has been adapted from Figure 6 in the article by Zhao et al beginning on page 2762.