From hypoxia single‐cell gene signatures to HIF targeting of AML leukemic stem cells

In their work, Velasco et al. revealed the gene expression signatures of over 100,000 primary blasts from AML patients of the most prevalent genetic subgroups. [...]this study represents a major resource to interrogate the molecular trajectories both within the AML cellular hierarchy (e.g., LSC versus non-LSC) and between diagnosis and relapse. Several strategies are currently explored to selectively interfere with the HIF transcription factors and multiple compounds were reported to inhibit HIF1a activity by various mechanisms including decreasing protein synthesis and/or expression, increasing degradation, interfering with heterodimerization, decreasing DNA binding, or interfering with transcriptional activation. [...]the significant intra- and interpatient differences in LSC gene expression signatures between diagnosis and relapse are now starting to be better characterized at the transcriptome and chromatin levels. [...]a better understanding of the interplay between hypoxia-mediated HIF activation consequences and other cellular processes, including mitochondria/metabolism or other transcriptional/epigenetic regulatory mechanisms, will be important.