Title |
Targeting Wnt pathway in mantle cell lymphoma-initiating cells
|
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Published in |
Journal of Hematology & Oncology, June 2015
|
DOI | 10.1186/s13045-015-0161-1 |
Pubmed ID | |
Authors |
Rohit Mathur, Lalit Sehgal, Frank K. Braun, Zuzana Berkova, Jorge Romaguerra, Michael Wang, M. Alma Rodriguez, Luis Fayad, Sattva S. Neelapu, Felipe Samaniego |
Abstract |
Mantle cell lymphoma (MCL) is an aggressive and incurable form of non-Hodgkin's lymphoma. Despite initial intense chemotherapy, up to 50 % of cases of MCL relapse often in a chemoresistant form. We hypothesized that the recently identified MCL-initiating cells (MCL-ICs) are the main reason for relapse and chemoresistance of MCL. Cancer stem cell-related pathways such as Wnt could be responsible for their maintenance and survival. We isolated MCL-ICs from primary MCL cells on the basis of a defined marker expression pattern (CD34-CD3-CD45+CD19-) and investigated Wnt pathway expression. We also tested the potential of Wnt pathway inhibitors in elimination of MCL-ICs. We showed that MCL-ICs are resistant to genotoxic agents vincristine, doxorubicin, and the newly approved Burton tyrosine kinase (BTK) inhibitor ibrutinib. We confirmed the differential up-regulation of Wnt pathway in MCL-ICs. Indeed, MCL-ICs were particularly sensitive to Wnt pathway inhibitors. Targeting β-catenin-TCF4 interaction with CCT036477, iCRT14, or PKF118-310 preferentially eliminated the MCL-ICs. Our results suggest that Wnt signaling is critical for the maintenance and survival of MCL-ICs, and effective MCL therapy should aim to eliminate MCL-ICs through Wnt signaling inhibitors. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 1 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 1 | 2% |
Unknown | 42 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Master | 9 | 21% |
Researcher | 5 | 12% |
Other | 4 | 9% |
Student > Bachelor | 4 | 9% |
Student > Doctoral Student | 4 | 9% |
Other | 9 | 21% |
Unknown | 8 | 19% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 13 | 30% |
Biochemistry, Genetics and Molecular Biology | 11 | 26% |
Pharmacology, Toxicology and Pharmaceutical Science | 2 | 5% |
Agricultural and Biological Sciences | 2 | 5% |
Unspecified | 1 | 2% |
Other | 6 | 14% |
Unknown | 8 | 19% |