Scientific Advances: Gene editing to model the clonal evolution of acute myeloid leukemia

To model malignant transformation in the lab, CRISPR/Cas9 was used to introduced three cancer driver mutations in induced pluripotent stem cells (iPSCs). The modified iPSCs were then subjected to hematopoietic differentiation. Remarkably, the cells mimicked the three distinct stages of malignant transformation as a consequence of the introduced mutation(s): 1) clonal hematopoiesis (ASXL1), 2) myelodysplastic syndrome (ASXL1 + SRFS2), and 3) leukemia (ASXL1 + SRFS2 + NRAS). The modeling of leukemic transformation enabled the analysis of transcriptome and chromatin landscape changes, resulting in the identification of potential novel drug targets in dysregulated cell autonomous inflammatory signaling.

For more information, see:
Wang, T., et al. (2021) Sequential CRISPR gene editing in human iPSCs charts the clonal evolution of myeloid leukemia and identifies early disease targets. Cell Stem Cell. https://doi.org/10.1016/j.stem.2021.01.011.

Keywords: CRISPR, Acute Myeloid Leukemia, IPSC, Malignant Transformation, Modeling

Questions? Email: crispr@amsterdamumc.nl