Go to
JCI Insight
Citations to this article
Christian Schürch, … , Alexandar Tzankov, Adrian F. Ochsenbein
Published January 9, 2012
Citation Information: J Clin Invest. 2012;122(2):624-638. https://doi.org/10.1172/JCI45977.
Citation Information: J Clin Invest. 2012;122(2):624-638. https://doi.org/10.1172/JCI45977.
Abstract
Chronic myelogenous leukemia (CML) results from a chromosomal translocation in hematopoietic stem or early progenitor cells that gives rise to the oncogenic BCR/ABL fusion protein. Clinically, CML has a chronic phase that eventually evolves into an accelerated stage and blast crisis. A CML-specific immune response is thought to contribute to the control of disease. Whether the immune system can also promote disease progression is not known. In the present study, we investigated the possibility that the TNF receptor family member CD27 is present on leukemia stem cells (LSCs) and mediates effects of the immune system on CML. In a mouse model of CML, BCR/ABL+ LSCs and leukemia progenitor cells were found to express CD27. Binding of CD27 by its ligand, CD70, increased expression of Wnt target genes in LSCs by enhancing nuclear localization of active β-catenin and TRAF2- and NCK-interacting kinase (TNIK). This resulted in increased proliferation and differentiation of LSCs. Blocking CD27 signaling in LSCs delayed disease progression and prolonged survival. Furthermore, CD27 was expressed on CML stem/progenitor cells in the bone marrow of CML patients, and CD27 signaling promoted growth of BCR/ABL+ human leukemia cells by activating the Wnt pathway. Since expression of CD70 is limited to activated lymphocytes and dendritic cells, our results reveal a mechanism by which adaptive immunity contributes to leukemia progression. In addition, targeting CD27 on LSCs may represent an attractive therapeutic approach to blocking the Wnt/β-catenin pathway in CML.
Authors
Christian Schürch, Carsten Riether, Matthias S. Matter, Alexandar Tzankov, Adrian F. Ochsenbein
Total citations by year
Citation information
Citations to this article (59)
| Title and authors | Publication | Year |
|---|---|---|
|
Inflammation and cancer cell survival: TRAF2 as a key player
Albini A, Di Paola L, Mei G, Baci D, Fusco N, Corso G, Noonan D |
Cell Death & Disease | 2025 |
|
Immune checkpoints regulate acute myeloid leukemia stem cells.
Reinhardt C, Ochsenbein AF |
Leukemia | 2025 |
|
Causal Effects of Immune Cells on Reproductive Ill-Health, Including Abnormal Spermatozoa, Polycystic Ovary Syndrome and Spontaneous Abortion: Mendelian Randomization Analyses
Chen S, Sun S, Zhou Z, Zhou Z, Zhang R, Song W, Xin H, Yang Q, Dai S, Huang K, Niu W, Shi H, Guo Y |
Journal of Multidisciplinary Healthcare | 2025 |
|
Simultaneous Expression of CD70 and POSTN in Cancer-Associated Fibroblasts Predicts Worse Survival of Colorectal Cancer Patients
Komura M, Wang C, Ito S, Kato S, Ueki A, Ebi M, Ogasawara N, Tsuzuki T, Kasai K, Kasugai K, Takiguchi S, Takahashi S, Inaguma S |
International journal of molecular sciences | 2024 |
|
Cancer stem cells: advances in knowledge and implications for cancer therapy
Chu X, Tian W, Ning J, Xiao G, Zhou Y, Wang Z, Zhai Z, Tanzhu G, Yang J, Zhou R |
Signal Transduction and Targeted Therapy | 2024 |
|
TNIK in disease: from molecular insights to therapeutic prospects.
Wu X, Zhang Z, Qiu Z, Wu X, Chen J, Liu L, Liu X, Zhao S, Yang Y, Zhao Y |
Apoptosis : an international journal on programmed cell death | 2024 |
|
Novel treatment strategies for chronic myeloid leukemia
Cruz-Rodriguez N, Deininger MW |
Blood | 2024 |
|
CD70 and PD‐L1 (CD274) co‐expression predicts poor clinical outcomes in patients with pleural mesothelioma
Inaguma S, Ueki A, Lasota J, Komura M, Sheema AN, Czapiewski P, Langfort R, Rys J, Szpor J, Waloszczyk P, Okoń K, Biernat W, Schrump DS, Hassan R, Miettinen M, Takahashi S |
The Journal of Pathology: Clinical Research | 2023 |
|
Targeting Wnt/β-Catenin Pathway by Flavonoids: Implication for Cancer Therapeutics
Pandey P, Khan F, Seifeldin SA, Alshaghdali K, Siddiqui S, Abdelwadoud ME, Vyas M, Saeed M, Mazumder A, Saeed A |
Nutrients | 2023 |
|
A global database for modeling tumor-immune cell communication.
Xie Y, Zhou W, Shi J, Xu M, Lin Z, Li D, Li J, Cheng S, Shao T, Xu J |
Scientific Data | 2023 |
|
Comprehensive Analysis of Expression and Pathway for CD27 in Esophageal Cancer.
Xiao FK, Wang L |
Molecular Biotechnology | 2023 |
|
Signaling pathways governing the behaviors of leukemia stem cells
Azizidoost S, Nasrolahi A, Sheykhi-Sabzehpoush M, Anbiyaiee A, Khoshnam SE, Farzaneh M, Uddin S |
Genes & Diseases | 2023 |
|
Immune checkpoints represent a promising breakthrough in targeted therapy and prognosis of myelodysplastic syndrome
Guo X, Yu S, Ren X, Li L |
Heliyon | 2023 |
|
A novel fluorescent dye selectively images and kills cancer stem cells by targeting mitochondria: Evidence from a cell line‑based zebrafish xenograft model
Ren T, Yang MZ, Zhang WM, Qin LJ, Zhou SC, Cheng NN, Huang YJ, Sun J, Xu N, Sun HB, Zhang BB |
Oncology Letters | 2023 |
|
A conserved ZFX/WNT3 axis modulates the growth and imatinib response of chronic myeloid leukemia stem/progenitor cells
Zhang X, Wang Y, Lu J, Xiao L, Chen H, Li Q, Li YY, Xu P, Ruan C, Zhou H, Zhao Y |
Cellular & Molecular Biology Letters | 2023 |
|
Eliminating chronic myeloid leukemia stem cells by IRAK1/4 inhibitors
Y Tanaka, R Takeda, T Fukushima, K Mikami, S Tsuchiya, M Tamura, K Adachi, T Umemoto, S Asada, N Watanabe, S Morishita, M Imai, M Nagata, M Araki, H Takizawa, T Fukuyama, C Lamagna, E Masuda, R Ito, S Goyama, N Komatsu, T Takaku, T Kitamura |
Nature Communications | 2022 |
|
Mechanism underlying the immune checkpoint inhibitor-induced hyper-progressive state of cancer
P Ding, L Wen, F Tong, R Zhang, Y Huang, X Dong |
2022 | |
|
The CD70-CD27 axis in oncology: the new kids on the block
Flieswasser T, Van den Eynde A, Van Audenaerde J, De Waele J, Lardon F, Riether C, de Haard H, Smits E, Pauwels P, Jacobs J |
Journal of experimental & clinical cancer research : CR | 2022 |
|
Quercetin Inhibits KBM7R Cell Proliferation through Wnt/β-Catenin Signaling.
Li W, Yu Y, Cheng H, Liu S, Gong T, Ma J, Tang Q |
Evidence-based complementary and alternative medicine : eCAM | 2022 |
|
TNF Receptor Associated Factor 2 (TRAF2) Signaling in Cancer.
Siegmund D, Wagner J, Wajant H |
Cancers | 2022 |
|
Signaling pathways and targeted therapies in lung squamous cell carcinoma: mechanisms and clinical trials
Niu Z, Jin R, Zhang Y, Li H |
Signal Transduction and Targeted Therapy | 2022 |
|
Ex Vivo Expansion of Phenotypic and Transcriptomic Chronic Myeloid Leukemia Stem Cells
Patel SB, Kuznetsova V, Matkins VR, Franceski AM, Bassal MA, Welner RS |
Experimental hematology | 2022 |
|
Direct conversion of osteosarcoma to adipocytes by targeting TNIK
Toru Hirozane, Mari Masuda, Teppei Sugano, Tetsuya Sekita, Naoko Goto, Toru Aoyama, Takato Sakagami, Yuko Uno, Hideki Moriyama, Masaaki Sawa, Naofumi Asano, Masaya Nakamura, Morio Matsumoto, Robert Nakayama, Tadashi Kondo, Akira Kawai, Eisuke Kobayashi, Tesshi Yamada |
JCI Insight | 2021 |
|
Tnfrsf4-expressing regulatory T cells promote immune escape of chronic myeloid leukemia stem cells
Magdalena Hinterbrandner, Viviana Rubino, Carina Stoll, Stefan Forster, Noah Schnüriger, Ramin Radpour, Gabriela M. Baerlocher, Adrian F. Ochsenbein, Carsten Riether |
JCI Insight | 2021 |
|
Targeting Leukemic Stem Cells in Chronic Myeloid Leukemia: Is It Worth the Effort?
S Soverini, SD Santis, C Monaldi, S Bruno, M Mancini |
International journal of molecular sciences | 2021 |
|
LIGHT/LTβR signaling regulates self-renewal and differentiation of hematopoietic and leukemia stem cells
SS Höpner, A Raykova, R Radpour, MA Amrein, D Koller, GM Baerlocher, C Riether, AF Ochsenbein |
Nature Communications | 2021 |
|
TNIK is a therapeutic target in Lung Squamous Cell Carcinoma and regulates FAK activation through Merlin.
Torres-Ayuso P, An E, Nyswaner KM, Bensen RC, Ritt DA, Specht SI, Das S, Andresson T, Cachau RE, Liang RJ, Ries AL, Robinson CM, Difilippantonio S, Gouker B, Bassel L, Karim BO, Miller CJ, Turk BE, Morrison DK, Brognard J |
Cancer Discovery | 2021 |
|
Declaration of Bcr-Abl1 independence
H Zhao, MW Deininger |
Leukemia | 2020 |
|
TNIK signaling imprints CD8+ T cell memory formation early after priming
CA Jaeger-Ruckstuhl, M Hinterbrandner, S Höpner, CE Correnti, U Lüthi, O Friedli, S Freigang, MF Sayed, ED Bührer, MA Amrein, CM Schürch, R Radpour, C Riether, AF Ochsenbein |
Nature Communications | 2020 |
|
The tumor-promoting effects of the adaptive immune system: a cause of hyperprogressive disease in cancer?
F Marcucci, C Rumio |
Cellular and Molecular Life Sciences | 2020 |
|
Druggable Biochemical Pathways and Potential Therapeutic Alternatives to Target Leukemic Stem Cells and Eliminate the Residual Disease in Chronic Myeloid Leukemia
F Muselli, JF Peyron, D Mary |
International journal of molecular sciences | 2019 |
|
Epigenetic Reprogramming and Emerging Epigenetic Therapies in CML
J Bugler, R Kinstrie, MT Scott, D Vetrie |
Frontiers in Cell and Developmental Biology | 2019 |
|
Detecting the stable point of therapeutic effect of chronic myeloid leukemia based on dynamic network biomarkers
J Xu, M Wu, S Zhu, J Lei, J Gao |
BMC bioinformatics | 2019 |
|
Immune checkpoint blockade and CAR-T cell therapy in hematologic malignancies
H Wang, G Kaur, AI Sankin, F Chen, F Guan, X Zang |
Journal of Hematology & Oncology | 2019 |
|
CD70 expression correlates with a worse prognosis in malignant pleural mesothelioma patients via immune evasion and enhanced invasiveness
S Inaguma, J Lasota, P Czapiewski, R Langfort, J Rys, J Szpor, P Waloszczyk, K Okoń, W Biernat, DS Schrump, R Hassan, K Kasai, M Miettinen, H Ikeda |
The Journal of Pathology | 2019 |
|
Therapeutic Antibodies for Myeloid Neoplasms—Current Developments and Future Directions
CM Schürch |
Frontiers in Oncology | 2018 |
|
Dynamics of angiogenesis in ischemic areas of the infarcted heart
K Kobayashi, K Maeda, M Takefuji, R Kikuchi, Y Morishita, M Hirashima, T Murohara |
Scientific Reports | 2017 |
|
Biological Networks and Pathway Analysis
TV Tatarinova, Y Nikolsky |
Biological Networks and Pathway Analysis | 2017 |
|
Cellular and Molecular Networks in Chronic Myeloid Leukemia: The Leukemic Stem, Progenitor and Stromal Cell Interplay
D Perrotti, G Silvestri, L Stramucci, J Yu, R Trotta |
Current drug targets | 2017 |
|
CD27 marks murine embryonic hematopoietic stem cells and type II prehematopoietic stem cells
Y Li, L Gao, B Hadland, K Tan, NA Speck |
Blood | 2017 |
|
Synergistic inhibition effect of TNIK inhibitor KY-05009 and receptor tyrosine kinase inhibitor dovitinib on IL-6-induced proliferation and Wnt signaling pathway in human multiple myeloma cells
Y Lee, JI Jung, KY Park, SA Kim, J Kim |
Oncotarget | 2017 |
|
The deubiquitinating enzyme USP48 stabilizes TRAF2 and reduces E-cadherin-mediated adherens junctions
S Li, D Wang, J Zhao, NM Weathington, D Shang, Y Zhao |
The FASEB Journal | 2017 |
|
CD70/CD27 signaling promotes blast stemness and is a viable therapeutic target in acute myeloid leukemia
C Riether, CM Schürch, ED Bührer, M Hinterbrandner, AL Huguenin, S Hoepner, I Zlobec, T Pabst, R Radpour, AF Ochsenbein |
Journal of Experimental Medicine | 2016 |
|
The Wnt signaling pathway in cancer
Y Duchartre, YM Kim, M Kahn |
Critical Reviews in Oncology/Hematology | 2016 |
|
Aberrant Wnt Signaling in Leukemia
F Staal, F Famili, LG Perez, K Pike-Overzet |
Cancers | 2016 |
|
β-Catenin is required for intrinsic but not extrinsic BCR-ABL1 kinase-independent resistance to tyrosine kinase inhibitors in chronic myeloid leukemia
AM Eiring, JS Khorashad, DJ Anderson, F Yu, HM Redwine, CC Mason, KR Reynolds, PM Clair, KC Gantz, TY Zhang, AD Pomicter, IL Kraft, AD Bowler, K Johnson, MM Partlin, T O'Hare, MW Deininger |
Leukemia | 2015 |
|
Organization of TNIK in dendritic spines: Tnik localization in the mouse brain
AC Burette, KD Phend, S Burette, Q Lin, M Liang, G Foltz, N Taylor, Q Wang, NJ Brandon, B Bates, MD Ehlers, RJ Weinberg |
The Journal of Comparative Neurology | 2015 |
|
Fbxo3-Dependent Fbxl2 Ubiquitination Mediates Neuropathic Allodynia through the TRAF2/TNIK/GluR1 Cascade
TB Lin, MC Hsieh, CY Lai, JK Cheng, YP Chau, T Ruan, GD Chen, HY Peng |
The Journal of neuroscience : the official journal of the Society for Neuroscience | 2015 |
|
Targeting tumor-necrosis factor receptor pathways for tumor immunotherapy
DA Schaer, D Hirschhorn-Cymerman, JD Wolchok |
Journal for ImmunoTherapy of Cancer | 2014 |
|
Regulation of hematopoietic and leukemic stem cells by the immune system
C Riether, CM Schürch, AF Ochsenbein |
Cell Death and Differentiation | 2014 |
|
Dendritic Cell-Based Immunotherapy for Myeloid Leukemias
CM Schürch, C Riether, AF Ochsenbein |
Frontiers in immunology | 2013 |
|
Targeting self-renewal pathways in myeloid malignancies
WA Sands, M Copland, H Wheadon |
Cell Communication and Signaling | 2013 |
|
Cytotoxic T cells induce proliferation of chronic myeloid leukemia stem cells by secreting interferon-γ
C Schürch, C Riether, MA Amrein, AF Ochsenbein |
Journal of Experimental Medicine | 2013 |
|
Emerging therapeutic strategies for targeting chronic myeloid leukemia stem cells
A Hamad, Z Sahli, ME Sabban, M Mouteirik, R Nasr |
Stem Cells International | 2013 |
|
Osteoclast precursors in murine bone marrow express CD27 and are impeded in osteoclast development by CD70 on activated immune cells
Y Xiao, JY Song, TJ de Vries, C Fatmawati, DB Parreira, GE Langenbach, N Babala, MA Nolte, V Everts, J Borst |
Proceedings of the National Academy of Sciences | 2013 |
|
Pushing the limits of targeted therapy in chronic myeloid leukaemia
T O'Hare, MS Zabriskie, AM Eiring, MW Deininger |
Nature Reviews Cancer | 2012 |
|
Targeting Chronic Myeloid Leukemia Stem Cells
R Kinstrie, M Copland |
Current Hematologic Malignancy Reports | 2012 |
|
The Germinal Center Kinase TNIK Is Required for Canonical NF-κB and JNK Signaling in B-Cells by the EBV Oncoprotein LMP1 and the CD40 Receptor
A Shkoda, JA Town, J Griese, M Romio, H Sarioglu, T Knöfel, F Giehler, A Kieser |
PLoS Biology | 2012 |
|
Modulating CD27 signaling to treat cancer
C Riether, CM Schürch, AF Ochsenbein |
OncoImmunology | 2012 |
Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)