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Citations to this article

CD27 signaling on chronic myelogenous leukemia stem cells activates Wnt target genes and promotes disease progression
Christian Schürch, … , Alexandar Tzankov, Adrian F. Ochsenbein
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.
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Research Article Hematology Article has an altmetric score of 5

CD27 signaling on chronic myelogenous leukemia stem cells activates Wnt target genes and promotes disease progression

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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

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 Total
Citations: 3 4 8 7 5 3 5 1 6 3 3 2 5 4 59
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2013 (5)

Title and authors Publication Year
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

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