leukemia stem cells

[Stem Cell Research] Investigators discuss the lessons that can be learned about the leukemia stem cell (LSC) state, its plasticity, stability and genetic and epigenetic determinants from induced pluripotent stem cell (iPSC) modeling. They also discuss the practical and translational implications of exploiting acute myeloid leukemia (AML)-iPSCs to prospectively isolate large numbers of iLSCs for large-scale experiments, such as screens, and for discovery of new therapeutic targets specific to AML LSCs.

[Nature Communications] Researchers showed that Dynole 34-2, a potent inhibitor of Dynamin GTPase activity, could block transduction of key signaling pathways and overcome chemoresistance of leukemia stem cells.

[Nature Communications] Investigators showed that a knock-in reporter mouse for the stem cell gene Musashi 2 allowed identification of leukemia stem cells in aggressive myeloid malignancies, and provided a strategy for defining their core dependencies.

[Blood] Using a genome-wide CRISPR-Cas9 screen for effectors of CC-90009 response, researchers uncovered the ILF2 and ILF3 heterodimeric complex as a novel regulator of cereblon expression. Knockout of ILF2/ILF3 decreased the production of full-length cereblon protein via modulating CRBN mRNA alternative splicing, leading to diminished response to CC-90009.

[Cell Death & Disease] Investigators addressed the consequences of spleen tyrosine kinase (SYK) inhibition to leukemia stem-cell function and assessed SYK-associated pathways in acute myeloid leukemia cell biology.

[Experimental and Molecular Medicine] Scientists discuss molecular maintenance in leukemia stem cells in chronic myeloid leukemia and provide a more in-depth discussion of the dual-specificity kinase DYRK2, which has been identified as a novel actionable checkpoint in a critical leukemic network.