The neuropeptide receptor calcitonin receptor-like (CALCRL) is a potential therapeutic target in acute myeloid leukemia
| Autor: | Wolfgang Hiddemann, Eike Bormann, Christoph Schliemann, Caroline Pabst, Linus Angenendt, Tobias Herold, Guy Sauvageau, Maria Francisca Arteaga, Klaus H. Metzeler, Klaus Wethmar, Wolfgang E. Berdel, Hubert Serve, Vijay Alla, Jan-Henrik Mikesch, Carsten Müller-Tidow, Georg Lenz, Kim Dohlich, Bob Löwenberg, Wolfgang Hartmann, Torsten Kessler, Adrian Angenendt, Matthias Stelljes, Rolf M. Mesters, Peter J. M. Valk, Karsten Spiekermann, Josée Hébert, Dennis Görlich, Stefan K. Bohlander, Utz Krug, Christian Schwöppe, M Christina Sauerland, Bernhard Wörmann, Leonie Braun, Maja Rothenberg-Thurley |
|---|---|
| Přispěvatelé: | Hematology |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Adult
Male 0301 basic medicine Cancer Research Myeloid Angiogenesis Biopsy Antineoplastic Agents Mice Young Adult 03 medical and health sciences 0302 clinical medicine Biomarkers Tumor medicine Animals Humans Molecular Targeted Therapy Calcitonin receptor Aged Aged 80 and over business.industry Calcitonin Receptor-Like Protein Genetic Variation Myeloid leukemia Hematology CALCRL Middle Aged medicine.disease Immunohistochemistry Leukemia Myeloid Acute Leukemia 030104 developmental biology medicine.anatomical_structure Oncology Calcitonin 030220 oncology & carcinogenesis Cancer research Female business Follow-Up Studies |
| Zdroj: | Leukemia 33, 2830-2841 (2019) Leukemia, 33(12), 2830-2841. Nature Publishing Group |
| ISSN: | 0887-6924 |
| Popis: | Calcitonin receptor-like (CALCRL) is a G-protein-coupled neuropeptide receptor involved in the regulation of blood pressure, angiogenesis, cell proliferation, and apoptosis, and is currently emerging as a novel target for the treatment of migraine. This study characterizes the role of CALCRL in acute myeloid leukemia (AML). We analyzed CALCRL expression in collectively more than 1500 well-characterized AML patients from five international cohorts (AMLCG, HOVON, TCGA, Leucegene, and UKM) and evaluated associations with survival. In the AMLCG analytic cohort, increasing transcript levels of CALCRL were associated with decreasing complete remission rates (71.5%, 53.7%, 49.6% for low, intermediate, high CALCRL expression), 5-year overall (43.1%, 26.2%, 7.1%), and event-free survival (29.9%, 15.8%, 4.7%) (all P < 0.001). CALCRL levels remained associated with all endpoints on multivariable regression analyses. The prognostic impact was confirmed in all validation sets. Genes highly expressed in CALCRLhigh AML were significantly enriched in leukemic stem cell signatures and CALCRL levels were positively linked to the engraftment capacity of primary patient samples in immunocompromised mice. CRISPR- Cas9-mediated knockout of CALCRL significantly impaired colony formation in human myeloid leukemia cell lines. Overall, our study demonstrates that CALCRL predicts outcome beyond existing risk factors and is a potential therapeutic target in AML. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink