Keep Current with the Latest in Cell Biology Research

Inflammation-Driven Deaminase Deregulation Fuels Human Pre-Leukemia Stem Cell Evolution

Comparative whole-genome and whole-transcriptome sequencing analyses of FACS-purified pre-leukemia stem cells from myeloproliferative neoplasm patients reveal APOBEC3C upregulation, an increased C-to-T mutational burden, and hematopoietic stem and progenitor cell proliferation during progression, which can be recapitulated by lentiviral APOBEC3C overexpression.
[Cell Reports]
Jiang, Q., Isquith, J., Ladel, L., Mark, A., Holm, F., Mason, C., He, Y., Mondala, P., Oliver, I., Pham, J., Ma, W., Reynoso, E., Ali, S., Morris, I. J., Diep, R., Nasamran, C., Xu, G., Sasik, R., Rosenthal, S. B., … Jamieson, C. (2021). Inflammation-driven deaminase deregulation fuels human pre-leukemia stem cell evolution. Cell Reports, 34(4). https://doi.org/10.1016/j.celrep.2020.108670 Cite
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Metoclopramide Treatment Blocks CD93-Signaling-Mediated Self-Renewal of Chronic Myeloid Leukemia Stem Cells

The authors identified CD93 as an important regulator of self-renewal and proliferation of murine and human leukemia stem cells, but not hematopoietic stem cells.
[Cell Reports]
Riether, C., Radpour, R., Kallen, N. M., Bürgin, D. T., Bachmann, C., Schürch, C. M., Lüthi, U., Arambasic, M., Hoppe, S., Albers, C. E., Baerlocher, G. M., & Ochsenbein, A. F. (2021). Metoclopramide treatment blocks CD93-signaling-mediated self-renewal of chronic myeloid leukemia stem cells. Cell Reports, 34(4). https://doi.org/10.1016/j.celrep.2020.108663 Cite
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AzurRx BioPharma Adds Two New Clinical Trial Sites in Europe for Phase IIb OPTION 2 Extension Study of MS1819 Immediate-Release Capsules in Cystic Fibrosis Patients

AzurRx BioPharma, Inc announced the activation of two additional clinical trial sites in Poland for the extension arm of the Phase IIb OPTION 2 study investigating immediate-release capsules of MS1819 for the treatment of exocrine pancreatic insufficiency in patients with cystic fibrosis.
[AzurRx BioPharma, Inc.]
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Understanding of the Crosstalk between Normal Residual Hematopoietic Stem Cells and the Leukemic Niche in Acute Myeloid Leukemia

Investigators present evidence of the key role of the bone marrow niche in suppressing HSCs during leukemic progression and provide perspectives on how future research in this topic may be exploited to provide treatments for one of the key complications of acute myeloid leukemia.
[Experimental Hematology]
Batsivari, A., Grey, W., & Bonnet, P. D. (2021). Understanding of the crosstalk between normal residual hematopoietic stem cells and the leukemic niche in Acute Myeloid Leukemia. Experimental Hematology, 0(0). https://doi.org/10.1016/j.exphem.2021.01.004 Cite
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Conserved Regulatory Logic at Accessible and Inaccessible Chromatin during the Acute Inflammatory Response in Mammals

Investigators report the identification of a set of NF-κB-bound elements and common chromatin landscapes underlying the acute inflammatory response across cell-types and mammalian species.
[Nature Communications]
Alizada, A., Khyzha, N., Wang, L., Antounians, L., Chen, X., Khor, M., Liang, M., Rathnakumar, K., Weirauch, M. T., Medina-Rivera, A., Fish, J. E., & Wilson, M. D. (2021). Conserved regulatory logic at accessible and inaccessible chromatin during the acute inflammatory response in mammals. Nature Communications, 12(1), 567. https://doi.org/10.1038/s41467-020-20765-1 Cite
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Immunicum AB (publ) Receives FDA Orphan Drug Designation for Ilixadencel as a Treatment of Soft Tissue Sarcoma (STS)

Immunicum AB announced that it has received Orphan Drug Designation (ODD) from the FDA for the company’s lead candidate, ilixadencel, a cell-based, off-the-shelf immune primer, for the treatment of Soft Tissue Sarcoma.
[Immunicum AB]
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Tumor-Suppressor Function of Beclin 1 in Breast Cancer Cells Requires E-Cadherin

Researchers performed a genome-wide CRISPR/Cas9 screen in MCF7 breast cancer cells to identify genes whose loss of function reversed Beclin 1-dependent inhibition of cellular proliferation.
[Proceedings of the National Academy of Sciences of the United States of America]
Wijshake, T., Zou, Z., Chen, B., Zhong, L., Xiao, G., Xie, Y., Doench, J. G., Bennett, L., & Levine, B. (2021). Tumor-suppressor function of Beclin 1 in breast cancer cells requires E-cadherin. Proceedings of the National Academy of Sciences, 118(5). https://doi.org/10.1073/pnas.2020478118 Cite
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Farnesyl Dimethyl Chromanol Targets Colon Cancer Stem Cells and Prevents Colorectal Cancer Metastasis

Investigators provided the first demonstration that farnesyl dimethyl chromanol inhibited colon cancer stem cell viability, survival, self-renewal, pluripotent transcription factors expression, organoids formation, and Wnt/β-catenin signalling, as evidenced by comparisons with vehicle-treated controls.
[Scientific Reports]
Wijshake, T., Zou, Z., Chen, B., Zhong, L., Xiao, G., Xie, Y., Doench, J. G., Bennett, L., & Levine, B. (2021). Tumor-suppressor function of Beclin 1 in breast cancer cells requires E-cadherin. Proceedings of the National Academy of Sciences, 118(5). https://doi.org/10.1073/pnas.2020478118 Cite
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The Irradiated Brain Microenvironment Supports Glioma Stemness and Survival via Astrocyte-Derived Transglutaminase 2

Extracellular matrix derived from irradiated astrocytes were found to be a major driver of this phenotype and astrocyte-derived transglutaminase 2 were identified as a promoter of glioma stemness and radioresistance.
[Cancer Research]
Berg, T. J., Marques, C., Pantazopoulou, V., Johansson, E., Stedingk, K. von, Lindgren, D., Jeannot, P., Pietras, E. J., Bergström, T., Swartling, F. J., Governa, V., Bengzon, J., Belting, M., Axelson, H., Squatrito, M., & Pietras, A. (2021). The irradiated brain microenvironment supports glioma stemness and survival via astrocyte-derived Transglutaminase 2. Cancer Research. https://doi.org/10.1158/0008-5472.CAN-20-1785 Cite
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Recent Updates on Chimeric Antigen Receptor T Cell Therapy for Hepatocellular Carcinoma

The authors summarize current chimeric antigen receptor T cell (CAR-T) therapy targets in the treatment of hepatocellular carcinoma (HCC), discuss current obstacles and possible solutions in the process, and describe potential strategies to improve the efficacy of CAR-T cells for patients with HCC.
[Cancer Gene Therapy]
Guo, J., & Tang, Q. (2021). Recent updates on chimeric antigen receptor T cell therapy for hepatocellular carcinoma. Cancer Gene Therapy, 1–13. https://doi.org/10.1038/s41417-020-00259-4 Cite
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TROAP Switches DYRK1 Activity to Drive Hepatocellular Carcinoma Progression

Mechanistic investigation revealed that trophinin-associated protein directly bound to dual specificity tyrosine phosphorylation regulated kinase 1A/B (DYRK1A/B), resulting in the cytoplasmic retention of proteins DYRK1A/B and promoting cell cycle process via activation of Akt/GSK-3β signaling.
[Cell Death & Disease]
Li, L., Wei, J.-R., Song, Y., Fang, S., Du, Y., Li, Z., Zeng, T.-T., Zhu, Y.-H., Li, Y., & Guan, X.-Y. (2021). TROAP switches DYRK1 activity to drive hepatocellular carcinoma progression. Cell Death & Disease, 12(1), 1–15. https://doi.org/10.1038/s41419-021-03422-3 Cite
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