OTS167 Blocks FLT3 Translation and Synergizes with FLT3 Inhibitors in FLT3 Mutant Acute Myeloid Leukemia

OTS167 alone or in combination with tyrosine kinase inhibitors were used to investigate the effect of OTS167 on FLT3 signaling and expression in human Fms-like tyrosine kinase 3 (FLT3) mutant acute myeloid leukemia cell lines and primary cells.
[Blood Cancer Journal]
Eisfelder, B. J., Saygin, C., Wynne, J., Colton, M. W., Fischietti, M., Beauchamp, E. M., Cheng, J. X., Odenike, O., Roboz, G., Alachkar, H., & Stock, W. (2021). OTS167 blocks FLT3 translation and synergizes with FLT3 inhibitors in FLT3 mutant acute myeloid leukemia. Blood Cancer Journal, 11(3), 1–15. https://doi.org/10.1038/s41408-021-00433-3 Cite
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Simultaneously Target of Normal and Stem Cells-Like Gastric Cancer Cells via Cisplatin and Anti-CD133 CAR-T Combination Therapy

Cisplatin and anti-CD133 chimeric antigen receptor T (CAR-T) combination treatment inhibited tumor progression in three different xenograft models with diminished CD133 positive stem cell-like cell infiltration.
[Cancer Immunology Immunotherapy]
Han, Y., Sun, B., Cai, H., & Xuan, Y. (2021). Simultaneously target of normal and stem cells-like gastric cancer cells via cisplatin and anti-CD133 CAR-T combination therapy. Cancer Immunology, Immunotherapy. https://doi.org/10.1007/s00262-021-02891-x Cite
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Epithelial–Mesenchymal Transition and Cancer Stem Cell Interactions in Breast Phyllodes Tumors: Immunohistochemical Evaluation of EZH2, EZR, HMGA2, CD24 and CD44 in Correlation with Outcome Analysis

Using tissue microarray sections, immunohistochemistry was performed on 360 PTs. Epithelial and stromal expressions of EZH2, EZR, HMGA2, CD24 and CD44 were evaluated to assess their impact on disease progression and behavior in correlation with clinicopathological parameters.
[Cancer Cell International]
Ahmed, S. S., Lim, J. C. T., Thike, A. A., Iqbal, J., & Tan, P. H. (2021). Epithelial–mesenchymal transition and cancer stem cell interactions in breast phyllodes tumours: immunohistochemical evaluation of EZH2, EZR, HMGA2, CD24 and CD44 in correlation with outcome analysis. Journal of Clinical Pathology. https://doi.org/10.1136/jclinpath-2020-207068 Cite
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Bortezomib Suppresses Self-Renewal and Leukemogenesis of Leukemia Stem Cell by NF-ĸB-Dependent Inhibition of CDK6 in MLL-Rearranged Myeloid Leukemia

Investigators found that bortezomib (bort) suppressed cell proliferation and decreased colony formation in human and murine leukemic blasts. Bort reduced the frequency and function of leukemia stem cells, inhibited the progression, and extended the overall survival in mixed‐lineage leukemia‐AF9‐transformed leukemic mice.
[Journal of Cellular and Molecular Medicine]
Zhou, B., Qin, Y., Zhou, J., Ruan, J., Xiong, F., Dong, J., Huang, X., Yu, Z., & Gao, S. (n.d.). Bortezomib suppresses self-renewal and leukemogenesis of leukemia stem cell by NF-ĸB-dependent inhibition of CDK6 in MLL-rearranged myeloid leukemia. Journal of Cellular and Molecular Medicine, n/a(n/a). https://doi.org/https://doi.org/10.1111/jcmm.16377 Cite
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National Marrow Donor Program/Be The Match Announce Plan to Launch ACCESS Clinical Trial

The National Marrow Donor Program®/Be The Match® announced plans to launch the ACCESS clinical trial titled “A Multicenter Phase II Trial of HLA-Mismatched Unrelated Donor Hematopoietic Cell Transplantation with Post-Transplantation Cyclophosphamide for Patients with Hematologic Malignancies.”
[The National Marrow Donor Program®]
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Identification of Leukemic and Pre-Leukemic Stem Cells by Clonal Tracking from Single-Cell Transcriptomics

Researchers demonstrated that leukemia stem cells, hematopoietic stem cells, and pre-leukemic stem cells could be identified and molecularly profiled by combining single-cell transcriptomics with lineage tracing using both nuclear and mitochondrial somatic variants.
[Nature Communications]
Velten, L., Story, B. A., Hernández-Malmierca, P., Raffel, S., Leonce, D. R., Milbank, J., Paulsen, M., Demir, A., Szu-Tu, C., Frömel, R., Lutz, C., Nowak, D., Jann, J.-C., Pabst, C., Boch, T., Hofmann, W.-K., Müller-Tidow, C., Trumpp, A., Haas, S., & Steinmetz, L. M. (2021). Identification of leukemic and pre-leukemic stem cells by clonal tracking from single-cell transcriptomics. Nature Communications, 12(1), 1366. https://doi.org/10.1038/s41467-021-21650-1 Cite
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TGFβ/Cyclin D1/Smad-Mediated Inhibition of BMP4 Promotes Breast Cancer Stem Cell Self-Renewal Activity

Investigators investigated the interplay and networking pathways occurring between TGFβ family ligands in regulating stemness in triple negative breast cancer (TNBC). They found that TGFβ stimulation of TNBCs resulted in enhanced tumorsphere formation efficiency and an increased proportion of the highly tumorigenic CD44high/CD24low cancer stem cell population.
[Oncogenesis]
Yan, G., Dai, M., Zhang, C., Poulet, S., Moamer, A., Wang, N., Boudreault, J., Ali, S., & Lebrun, J.-J. (2021). TGFβ/cyclin D1/Smad-mediated inhibition of BMP4 promotes breast cancer stem cell self-renewal activity. Oncogenesis, 10(3), 1–14. https://doi.org/10.1038/s41389-021-00310-5 Cite
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IL-17B/IL-17RB Signaling Cascade Contributes to Self-Renewal and Tumorigenesis of Cancer Stem Cells by Regulating Beclin-1 Ubiquitination

The authors found that IL-17RB expression was significantly upregulated in spheroid cells and Lgr5-positive cells from the same tumor tissues of patients with gastric cancer, which was closely correlated with the degree of cancer cell differentiation.
[Oncogene]
Bie, Q., Song, H., Chen, X., Yang, X., Shi, S., Zhang, L., Zhao, R., Wei, L., Zhang, B., Xiong, H., & Zhang, B. (2021). IL-17B/IL-17RB signaling cascade contributes to self-renewal and tumorigenesis of cancer stem cells by regulating Beclin-1 ubiquitination. Oncogene, 1–17. https://doi.org/10.1038/s41388-021-01699-4 Cite
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Inhibition of Bruton’s Tyrosine Kinase as a Therapeutic Strategy for Chemoresistant Oral Squamous Cell Carcinoma and Potential Suppression of Cancer Stemness

Researchers investigated the effects of Bruton’s tyrosine kinase (BTK) on oncurrent chemoradiotherapy-resistant oral squamous cell carcinoma tissues (OSCC). The effect of ibrutinib, a first-in-class BTK inhibitor, was tested on stem cell-like OSCC tumorspheres.
[Oncogenesis]
Liu, S.-C., Wu, Y.-C., Huang, C.-M., Hsieh, M.-S., Huang, T.-Y., Huang, C.-S., Hsu, T.-N., Huang, M.-S., Lee, W.-H., Yeh, C.-T., & Lin, C.-S. (2021). Inhibition of Bruton’s tyrosine kinase as a therapeutic strategy for chemoresistant oral squamous cell carcinoma and potential suppression of cancer stemness. Oncogenesis, 10(2), 1–18. https://doi.org/10.1038/s41389-021-00308-z Cite
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Electrospun Nanofiber Scaffolds for the Propagation and Analysis of Breast Cancer Stem Cells In Vitro

The authors developed a 3D culture platform that mimics the metastatic tumor extracellular matrix to effectively increase cancer stem cell (CSC) population in vitro and allow CSC analysis.
[Biomedical Materials]
Prieto, E. I., Mojares, E. B. A., Cortez, J. J. M., & Jr, M. R. V. (2021). Electrospun nanofiber scaffolds for the propagation and analysis of breast cancer stem cells in vitro. Biomedical Materials, 16(3), 035004. https://doi.org/10.1088/1748-605x/abc3dd Cite
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Functional Reconstruction of Human AML Reveals Stem Cell Origin and Vulnerability of Treatment-Resistant MLL-Rearranged Leukemia

HSC-derived Mixed Lineage Leukemia- acute myeloid leukemia gene fusions was highly resistant to chemotherapy and expressed elevated amounts of the multispecific anion transporter ABCC3.
[Science Translational Medicine]
Zeisig, B. B., Fung, T. K., Zarowiecki, M., Tsai, C. T., Luo, H., Stanojevic, B., Lynn, C., Leung, A. Y. H., Zuna, J., Zaliova, M., Bornhauser, M., Bonin, M. von, Lenhard, B., Huang, S., Mufti, G. J., & So, C. W. E. (2021). Functional reconstruction of human AML reveals stem cell origin and vulnerability of treatment-resistant MLL-rearranged leukemia. Science Translational Medicine, 13(582). https://doi.org/10.1126/scitranslmed.abc4822 Cite
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