SUMOylation Disassembles the Tetrameric Pyruvate Kinase M2 to Block Myeloid Differentiation of Leukemia Cells

Scientists found that SUMOylation of the M2 isoform of pyruvate kinase, a rate-limiting glycolytic enzyme catalyzing the dephosphorylation of phosphoenolpyruvate to pyruvate, is prevalent in a variety of leukemic cell lines as well as primary samples from patients with leukemia through multiple-reaction monitoring based targeted mass spectrometry analysis.
[Cell Death & Disease]
Xia, L., Jiang, Y., Zhang, X.-H., Wang, X.-R., Wei, R., Qin, K., & Lu, Y. (2021). SUMOylation disassembles the tetrameric pyruvate kinase M2 to block myeloid differentiation of leukemia cells. Cell Death & Disease, 12(1), 1–13. https://doi.org/10.1038/s41419-021-03400-9 Cite
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Dynamic Immune Profiling Identifies the Stronger Graft-Versus-Leukemia (GVL) Effects With Haploidentical Allografts Compared to HLA-Matched Stem Cell Transplantation

Researchers employed two nonirradiated leukemia mouse models which carried human AML-ETO or MLL-AF9 fusion gene to establish haplo-identical and major histocompatibility-matched transplantation models and investigated the immune cell dynamic response during leukemia development in vivo.
[Cellular & Molecular Immunology]
Guo, H., Chang, Y.-J., Hong, Y., Xu, L.-P., Wang, Y., Zhang, X.-H., Wang, M., Chen, H., Chen, Y.-H., Wang, F.-R., Wei-Han, Sun, Y.-Q., Yan, C.-H., Tang, F.-F., Mo, X.-D., Liu, K.-Y., & Huang, X.-J. (2021). Dynamic immune profiling identifies the stronger graft-versus-leukemia (GVL) effects with haploidentical allografts compared to HLA-matched stem cell transplantation. Cellular & Molecular Immunology, 1–14. https://doi.org/10.1038/s41423-020-00597-1 Cite
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Overcoming Target Epitope Masking Resistance that Can Occur on Low-Antigen-Expresser AML Blasts after IL-1RAP Chimeric Antigen Receptor T Cell Therapy Using the Inducible Caspase 9 Suicide Gene Safety Switch

As acute myeloid leukemia (AML) primary blasts express different levels of accessory protein of the interleukin-1 receptor (IL-1RAP), scientists modeled transduction of different AML tumor cell lines screened for density of antigenic sites with their lentiviral vectors carrying a third-generation IL-1RAP chimeric antigen receptor, an iCASP9 suicide gene, and a truncated CD19 surface gene.
[Cancer Gene Therapy]
Warda, W., Da Rocha, M. N., Trad, R., Haderbache, R., Salma, Y., Bouquet, L., Roussel, X., Nicod, C., Deschamps, M., & Ferrand, C. (2021). Overcoming target epitope masking resistance that can occur on low-antigen-expresser AML blasts after IL-1RAP chimeric antigen receptor T cell therapy using the inducible caspase 9 suicide gene safety switch. Cancer Gene Therapy, 1–11. https://doi.org/10.1038/s41417-020-00284-3 Cite
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Integrated Decoding Hematopoiesis and Leukemogenesis Using Single-Cell Sequencing and Its Medical Implication

Scientists analyzed ~200,000 single-cell transcriptomes of bone marrow mononuclear cells and its subsets from 23 clinical samples. They constructed a comprehensive cell atlas as hematopoietic reference.
[Cell Discovery]
Qin, P., Pang, Y., Hou, W., Fu, R., Zhang, Y., Wang, X., Meng, G., Liu, Q., Zhu, X., Hong, N., Cheng, T., & Jin, W. (2021). Integrated decoding hematopoiesis and leukemogenesis using single-cell sequencing and its medical implication. Cell Discovery, 7(1), 1–17. https://doi.org/10.1038/s41421-020-00223-4 Cite
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USP15 Deubiquitinase Safeguards Hematopoiesis and Genome Integrity in Hematopoietic Stem Cells and Leukemia Cells

The authors systematically inactivated deubiquitinating enzymes (DUBs) in mouse hematopoietic progenitors using in vivo small hairpin RNA (shRNA) screens. They found that multiple DUBs may be individually required for hematopoiesis and identify ubiquitin-specific protease 15 (USP15) as essential for hematopoietic stem cell maintenance in vitro and in transplantations and Usp15 knockout (KO) mice in vivo.
[Cell Reports]
USP15 Deubiquitinase Safeguards Hematopoiesis and Genome Integrity in Hematopoietic Stem Cells and Leukemia Cells: Cell Reports. (n.d.). Retrieved January 4, 2021, from https://www.cell.com/cell-reports/fulltext/S2211-1247(20)31522-9 Cite
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Bone Marrow Niche ATP Levels Determine Leukemia-Initiating Cell Activity via P2X7 in Leukemic Models

The authors showed that ATP levels were markedly increased in the bone marrow niches of mice with acute myeloid leukemia, and leukemia-initiating cells preferred to localizing to the endosteal niche with relatively high ATP levels, as indicated by a sensitive ATP indicator.
[Journal of Clinical Investigation]
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A Stem Cell Reporter Based Platform to Identify and Target Drug Resistant Stem Cells in Myeloid Leukemia

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.
[Nature Communications]
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Single Cell RNA-Seq Reveals Developmental Plasticity with Coexisting Oncogenic and Immune Evasion Programs in ETP-ALL

Fast-cycling stem-like leukemia cells demonstrated Notch activation and were effectively eliminated in patients by Notch inhibition, while slow cycling stem-like cells were Notch-independent but rather relied on PI3K signaling, likely explaining the poor efficacy of Notch inhibition in this disease.
[Blood]
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Pivotal Role of DPYSL2A in KLF4-Mediated Monocytic Differentiation of Acute Myeloid Leukemia Cells

The authors report that dihydropyrimidinase like 2 (DPYSL2), also known as CRMP2, was a novel key differentiation mediator downstream of KLF4 in acute myeloid leukemia cells.
[Scientific Reports]
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Dengue Virus Infection Impedes Megakaryopoiesis in MEG-01 Cells where the Virus Envelope Protein Interacts with the Transcription Factor TAL-1

Investigators studied Dengue virus infection of MEG-01 cells to understand its effect on megakaryopoiesis and the generation of platelet-like-particles.
[Scientific Reports]
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Induction of Differentiation of the Acute Myeloid Leukemia Cell Line (HL-60) by a Securinine Dimer

Scientists found that SN3-L6 induced transdifferentiation of both acute myeloid leukemia and chronic myelogenous leukemia cells but unexpectedly, a new transdifferentiation pathway from acute promyelocytic leukemia cells to morphologically and immunologically normal megakaryocytes and platelets were discovered.
[Cell Death Discovery]
Hou, W., Wang, Z.-Y., Lin, J., & Chen, W.-M. (2020). Induction of differentiation of the acute myeloid leukemia cell line (HL-60) by a securinine dimer. Cell Death Discovery, 6(1), 1–11. https://doi.org/10.1038/s41420-020-00354-3 Cite
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