Calcitonin receptor-like (CALCRL) is a marker of stemness and an independent predictor of outcome in pediatric AML
| Autor: | Claudia Rossig, Christoph Schliemann, Maria Francisca Arteaga, Linus Angenendt, Wolfgang E. Berdel, Marius Wöste, Georg Lenz, Soheil Meshinchi, Martin Dugas, Adrian Angenendt, Sarah Sandmann, Jan-Henrik Mikesch |
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| Rok vydání: | 2021 |
| Předmět: |
Oncology
medicine.medical_specialty Cohort Studies Recurrence hemic and lymphatic diseases Internal medicine White blood cell Biomarkers Tumor medicine Humans Cumulative incidence Calcitonin receptor Child neoplasms Myeloid Neoplasia business.industry Calcitonin Receptor-Like Protein Hazard ratio Myeloid leukemia Hematology CALCRL Receptors Calcitonin Confidence interval Leukemia Myeloid Acute medicine.anatomical_structure Calcitonin business |
| Zdroj: | Blood Advances |
| ISSN: | 2473-9537 2473-9529 |
| DOI: | 10.1182/bloodadvances.2021005236 |
| Popis: | Key Points Expression of CALCRL is an independent prognostic factor and a potential therapeutic target in pediatric AML.CALCRL is linked with relapse risk in p ediatric AML, which supports its role as a master regulator of relapse-initiating drug-tolerant cells. Visual Abstract We have recently identified the G protein-coupled neuropeptide receptor calcitonin receptor‐like (CALCRL) as an independent prognostic biomarker and a therapeutic target in more than 1500 adult patients with acute myeloid leukemia (AML). Here, we confirmed CALCRL expression as a prognostic factor in a cohort of 284 pediatric patients with AML. High CALCRL expression was independently associated with event-free survival (hazard ratio [HR], 1.87; 95% confidence interval [CI], 1.36-2.57; P = .0001), overall survival (HR, 1.55; 95% CI, 1.06-2.27; P = .025), and cumulative incidence of relapse (HR, 2.10; 95% CI, 1.49-1.96; P < .0001) when adjusting for age, white blood cell count, and genetic risk. Despite its association with leukemia stem cell signatures, CALCRL expression remained associated with all end points when compared with the 17-gene leukemic stem cell score. The strong association of CALCRL expression with the risk of relapse also in the pediatric population supports its role as novel age-independent master regulator of relapse-initiating, drug-tolerant AML cells in humans. |
| Databáze: | OpenAIRE |
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