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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Hematopoietic Cell Transplant in Pediatric Acute Myeloid Leukemia after Similar Upfront Therapy; A Comparison of Conditioning Regimens

Researchers retrospectively analyzed the impact of Busulfan–Cyclophosphamide, Busulfan–Cyclophosphamide–Melphalan and Clofarabine–Fludarabine–Busulfan in pediatric AML-patients, with similar upfront leukemia treatment, receiving an hematopoietic cell transplant between 2010 and 2015.
[Bone Marrow Transplantation]
Versluys, A. B., Boelens, J. J., Pronk, C., Lankester, A., Bordon, V., Buchner, J., Ifversen, M., Jackmann, N., Sundin, M., Vettenranta, K., Abrahamson, J., & Mellgren, K. (2021). Hematopoietic cell transplant in pediatric acute myeloid leukemia after similar upfront therapy; a comparison of conditioning regimens. Bone Marrow Transplantation, 1–7. https://doi.org/10.1038/s41409-020-01201-w Cite
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Vor Announces FDA Clearance of IND Application for VOR33

Vor Biopharma announced that the FDA has cleared the company’s Investigational New Drug (IND) application for VOR33, an engineered hematopoietic stem cell therapy candidate being developed for the treatment of acute myeloid leukemia.
[Vor Biopharma]
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Adrenomedullin-CALCRL Axis Controls Relapse-Initiating Drug Tolerant Acute Myeloid Leukemia Cells

Calcitonin receptor-like receptor (CALCRL) knockdown impaired leukemic growth, decreased leukemic stem cell frequency, and sensitized to cytarabine in patient-derived xenograft models.
[Nature Communications]
Larrue, C., Guiraud, N., Mouchel, P.-L., Dubois, M., Farge, T., Gotanègre, M., Bosc, C., Saland, E., Nicolau-Travers, M.-L., Sabatier, M., Serhan, N., Sahal, A., Boet, E., Mouche, S., Heydt, Q., Aroua, N., Stuani, L., Kaoma, T., Angenendt, L., … Sarry, J.-E. (2021). Adrenomedullin-CALCRL axis controls relapse-initiating drug tolerant acute myeloid leukemia cells. Nature Communications, 12(1), 422. https://doi.org/10.1038/s41467-020-20717-9 Cite
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Generation of a New Immortalized Human Lung Pericyte Cell Line: A Promising Tool for Human Lung Pericyte Studies

The authors established an immortalized human lung pericyte cell line. Developed using SV40 large T antigen lentivirus, immortalized pericytes exhibited stable SV40T expression, sustained proliferation, and had significantly higher telomerase activity compared to normal human lung pericytes.
[Laboratory Investigation]
Li, P., Wu, Y., Goodwin, A. J., Halushka, P. V., Wilson, C. L., Schnapp, L. M., & Fan, H. (2021). Generation of a new immortalized human lung pericyte cell line: a promising tool for human lung pericyte studies. Laboratory Investigation, 1–11. https://doi.org/10.1038/s41374-020-00524-y Cite
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GDF15 Promotes Glioma Stem Cell-Like Phenotype via Regulation of ERK1/2–C-Fos–LIF Signaling

The authors report that growth differentiation factor 15 (GDF15) promotes the glioma stem cell (GSC)-like phenotype in GSC-like cells through the activation of leukemia inhibitor factor (LIF)–STAT3 signaling.
[Cell Death Discovery]
Zhu, S., Yang, N., Guan, Y., Wang, X., Zang, G., Lv, X., Deng, S., Wang, W., Li, T., & Chen, J. (2021). GDF15 promotes glioma stem cell-like phenotype via regulation of ERK1/2–c-Fos–LIF signaling. Cell Death Discovery, 7(1), 1–12. https://doi.org/10.1038/s41420-020-00395-8 Cite
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CXCR5 CAR-T Cells Simultaneously Target B Cell Non-Hodgkin’s Lymphoma and Tumor-Supportive Follicular T Helper Cells

To target both B cell Non-Hodgkin’s lymphoma and follicular T helper cells in the tumor microenvironment, researchers applied a chimeric antigen receptor that recognized human CXCR5 with high avidity.
[Nature Communications]
Bunse, M., Pfeilschifter, J., Bluhm, J., Zschummel, M., Joedicke, J. J., Wirges, A., Stark, H., Kretschmer, V., Chmielewski, M., Uckert, W., Abken, H., Westermann, J., Rehm, A., & Höpken, U. E. (2021). CXCR5 CAR-T cells simultaneously target B cell non-Hodgkin’s lymphoma and tumor-supportive follicular T helper cells. Nature Communications, 12(1), 240. https://doi.org/10.1038/s41467-020-20488-3 Cite
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Targeting Leukemia-Initiating Cells in Acute Lymphoblastic Leukemia (ALL)

The authors review several biological and clinical aspects related to leukemia-initiating cells (LICs) in acute lymphoblastic leukemia (ALL), including: 1) immunophenotypic characterization of LIC-enriched subsets in human and mouse models of ALL; 2) emerging therapeutics against regulatory signaling pathways involved in LIC progression and maintenance in T- and B-cell leukemias; 3) novel epigenetic and age-related mechanisms of LIC propagation, and 4) ongoing efforts in immunotherapy to eradicate LIC-enriched cell subsets in relapsed and refractory ALL cases.
[Cancer Research]
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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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A Modular and Controllable T Cell Therapy Platform for Acute Myeloid Leukemia

Researchers developed a modular and controllable MHC-unrestricted adoptive T cell therapy platform tailored to acute myeloid leukemia.
[Leukemia]
Benmebarek, M.-R., Cadilha, B. L., Herrmann, M., Lesch, S., Schmitt, S., Stoiber, S., Darwich, A., Augsberger, C., Brauchle, B., Rohrbacher, L., Oner, A., Seifert, M., Schwerdtfeger, M., Gottschlich, A., Rataj, F., Fenn, N. C., Klein, C., Subklewe, M., Endres, S., … Kobold, S. (2021). A modular and controllable T cell therapy platform for acute myeloid leukemia. Leukemia, 1–15. https://doi.org/10.1038/s41375-020-01109-w 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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