DYRK2 Controls a Key Regulatory Network in Chronic Myeloid Leukemia Stem Cells

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.
[Experimental and Molecular Medicine]
Park, C. S., & Lacorazza, H. D. (2020). DYRK2 controls a key regulatory network in chronic myeloid leukemia stem cells. Experimental & Molecular Medicine, 1–10. https://doi.org/10.1038/s12276-020-00515-5 Cite
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Targeting Mitochondrial Respiration for the Treatment of Acute Myeloid Leukemia

Scientists discuss the relative dependency that acute myeloid leukemia (AML) cells have on mitochondrial function, and the ability to pivot this reliance to target important subsets of AML cells, including leukemia stem cells.
[Biochemical Pharmacology]
Carter, J. L., Hege, K., Kalpage, H. A., Edwards, H., Hüttemann, M., Taub, J. W., & Ge, Y. (2020). Targeting mitochondrial respiration for the treatment of acute myeloid leukemia. Biochemical Pharmacology, 114253. https://doi.org/10.1016/j.bcp.2020.114253 Cite
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The Role of Autophagy in Targeted Therapy for Acute Myeloid Leukemia

Scientists review studies on the role of autophagy in acute myeloid leukemia (AML) development and summarize the linkage between autophagy and several recurrent genetic abnormalities in AML, highlighting the potential of capitalizing on autophagy modulation in targeted therapy for AML.
[Autophagy]
Du, W., Xu, A., Huang, Y., Cao, J., Zhu, H., Yang, B., Shao, X., He, Q., & Ying, M. (2020). The role of autophagy in targeted therapy for acute myeloid leukemia. Autophagy, 0(0), 1–15. https://doi.org/10.1080/15548627.2020.1822628 Cite
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The Role of Autophagy in Targeted Therapy for Acute Myeloid Leukemia

Scientists review studies on the role of autophagy in acute myeloid leukemia (AML) development and summarize the linkage between autophagy and several recurrent genetic abnormalities in AML, highlighting the potential of capitalizing on autophagy modulation in targeted therapy for AML.
[Autophagy]
Du, W., Xu, A., Huang, Y., Cao, J., Zhu, H., Yang, B., Shao, X., He, Q., & Ying, M. (2020). The role of autophagy in targeted therapy for acute myeloid leukemia. Autophagy, 0(0), 1–15. https://doi.org/10.1080/15548627.2020.1822628 Cite
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Nicotinamide Metabolism Mediates Resistance to Venetoclax in Relapsed Acute Myeloid Leukemia Stem Cells

Detailed metabolomic analysis revealed elevated nicotinamide metabolism in relapsed leukemia stem cells (LSCs), which activated both amino acid metabolism and fatty acid oxidation to drive OXPHOS, thereby providing a means for LSCs to circumvent the cytotoxic effects of venetoclax and azacitidine therapy.
[Cell Stem Cell]
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Targeting CD70 with Cusatuzumab Eliminates Acute Myeloid Leukemia Stem Cells in Patients Treated with Hypomethylating Agents

Scientists demonstrated that leukemia stem cells upregulated the tumor necrosis factor family ligand CD70 in response to hypomethylating agent treatment resulting in increased CD70/CD27 signaling.
[Nature Medicine]
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Quantitative Proteomics Reveals Specific Metabolic Features of Acute Myeloid Leukemia Stem Cells

By comparing leukemic stem cells (LSCs) to leukemic blasts and healthy hematopoietic stem and progenitor cells (HSPCs), researchers validated candidate LSC markers and highlight novel and potentially targetable proteins that are absent or only lowly expressed in HSPCs.
[Blood]
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Targeting RSPO3-LGR4 Signaling for Leukemia Stem Cell Eradication in Acute Myeloid Leukemia

Scientists report that a positive modulator of canonical WNT signaling pathway, RSPO-LGR4, upregulates key self-renewal genes and is essential for leukemia stem cell self-renewal in a subset of acute myeloid leukemia.
[Cell Stem Cell]
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Targeting FTO Suppresses Cancer Stem Cell Maintenance and Immune Evasion

Researchers showed that genetic depletion and pharmacological inhibition of fat mass and obesity-associated protein dramatically attenuated leukemia stem/initiating cell self-renewal and reprogrammed immune response by suppressing expression of immune checkpoint genes, especially LILRB4.
[Cancer Cell]
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Acute Myeloid Leukemia iPSCs Reveal a Role for RUNX1 in the Maintenance of Human Leukemia Stem Cells

Researchers report that genetically clonal iPSCs derived from an acute myeloid leukemia patient and characterized by exceptionally high engraftment potential gave rise, upon hematopoietic differentiation, to a phenotypic hierarchy.
[Cell Reports]
Wesely, J., Kotini, A. G., Izzo, F., Luo, H., Yuan, H., Sun, J., Georgomanoli, M., Zviran, A., Deslauriers, A. G., Dusaj, N., Nimer, S. D., Leslie, C., Landau, D. A., Kharas, M. G., & Papapetrou, E. P. (2020). Acute Myeloid Leukemia iPSCs Reveal a Role for RUNX1 in the Maintenance of Human Leukemia Stem Cells. Cell Reports, 31(9). https://doi.org/10.1016/j.celrep.2020.107688 Cite
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Disrupting Mitochondrial Copper Distribution Inhibits Leukemic Stem Cell Self-Renewal

The authors found increased mRNA expression of mitochondrial intermembrane assembly pathway substrates in acute myeloid leukemia stem cells.
[Cell Stem Cell]
Ostrander, E. L., Kramer, A. C., Mallaney, C., Celik, H., Koh, W. K., Fairchild, J., Haussler, E., Zhang, C. R. C., & Challen, G. A. (2020). Divergent Effects of Dnmt3a and Tet2 Mutations on Hematopoietic Progenitor Cell Fitness. Stem Cell Reports, 0(0). https://doi.org/10.1016/j.stemcr.2020.02.011 Cite
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