Research Highlight #5: Leukemic stem cells from iPSCs

Today let’s delve into a curious case involving induced pluripotent stem cells (iPSCs) and leukemic stem cells (LSCs). Most blood cells derived from iPSCs are unable to engraft in immunodeficient mice. However, Wesely and colleagues observed an exceptionally high engraftment efficiency of cell lines derived from an individual affected by acute myeloid leukemia (AML). In particular, in vitro they observed typical round cells together with cobblestone-like, firmly adherent cells. The latter displayed markers of immaturity, a more quiescent cell cycle, but foremost they were responsible for the successful engraftment in immunodeficient mice. Collectively, these properties prompted the authors to identify the cells as induced Leukemic Stem Cells (iLSCs). They proved that the iLSCs can become the round cells, but not vice versa, suggesting a stem cell nature. In addition, the adherent phenotype allowed the easy separation of the two populations. In-depth transcriptomic analysis, both at single-cell and population level, was coupled with the study of chromatin accessibility. The iLSCs displayed a molecular resemblance to the leukemic stem cells isolated from AML patients, based on a 42-genes signature. Finally, the authors identified the transcription factor RUNX1 as critical for iLSC phenotype maintenance, as it is involved in the expression of 16 of the 42 genes in the LSC signature. In conclusion, this work describes for the first time the derivation of LSCs from iPSCs. This could be a fantastic tool for the study of the cancer stem cell theory, as those rare cells are not prospectively isolated, but only studied after transplantation. Since these iLSCs were derived from a single patient, it will be interesting to isolate them from other AML-iPSCs lines.

Wesely et al. “Acute Myeloid Leukemia iPSCs Reveal a Role for RUNX1 in the Maintenance of Human Leukemia Stem Cells”

Doi: https://doi.org/10.1016/j.celrep.2020.107688

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