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Updated: Mar 16, 2026
High-throughput Analysis of Mammalian Olfactory Receptors: Measurement of Receptor Activation via Luciferase Activity
Published on: June 2, 2014
Functional characterization of the ectopically expressed olfactory receptor 2AT4 in human myelogenous leukemia
S Manteniotis1, S Wojcik1, P Brauhoff1
1Department of Cell Physiology, Ruhr-University Bochum , Bochum, Germany.
Abstract:
The olfactory receptor (OR) family was found to be expressed mainly in the nasal epithelium. In the last two decades members of the OR family were detected to be functional expressed in different parts of the human body such as in liver, prostate or intestine cancer cells. Here, we detected the expression of several ORs in the human chronic myelogenous leukemia (CML) cell line K562 and in white blood cells of clinically diagnosed acute myeloid leukemia (AML) patients by RT-PCR and next-generation sequencing. With calcium-imaging, we characterized in greater detail the cell biological role of one OR (OR2AT4) in leukemia. In both cell systems, the OR2AT4 agonist Sandalore-evoked strong Ca(2+) influx via the adenylate cyclase-cAMP-mediated pathway. The OR2AT4 antagonist Phenirat prevented the Sandalore-induced intracellular Ca(2+) increase. Western blot and flow cytometric experiments revealed that stimulation of OR2AT4 reduced the proliferation by decreasing p38-MAPK phosphorylation and induced apoptosis via phosphorylation of p44/42-MAPK. Furthermore, Sandalore increased the number of hemoglobin-containing cells in culture. We described for the first time an OR-mediated pathway in CML and AML that can regulate proliferation, apoptosis and differentiation after activation. This mechanism offers novel therapeutic options for the treatment of AML.
Insights
Olfactory receptors (ORs) are expressed in leukemia cells, regulating proliferation and apoptosis. Targeting the OR2AT4 pathway with Sandalore offers new therapeutic strategies for acute myeloid leukemia (AML) and chronic myelogenous leukemia (CML).
Area of Science:
- Molecular Biology
- Oncology
- Immunology
Background:
- Olfactory receptors (ORs) are primarily in the nasal epithelium but have been found in various human cancer cells.
- Their role in hematological malignancies like leukemia is largely unexplored.
Purpose of the Study:
- To investigate the expression and function of ORs in chronic myelogenous leukemia (CML) and acute myeloid leukemia (AML) cells.
- To elucidate the cell biological role of olfactory receptor 2AT4 (OR2AT4) in leukemia.
Main Methods:
- Reverse transcription-polymerase chain reaction (RT-PCR) and next-generation sequencing to detect OR expression.
- Calcium imaging to assess cellular responses.
- Western blot and flow cytometry to analyze proliferation, apoptosis, and differentiation markers.
Main Results:
- Several ORs were detected in K562 (CML) cells and AML patient white blood cells.
- The OR2AT4 agonist Sandalore induced calcium influx via the adenylate cyclase-cAMP pathway, which was blocked by the antagonist Phenirat.
- OR2AT4 stimulation reduced proliferation (decreasing p38-MAPK phosphorylation), induced apoptosis (via p44/42-MAPK phosphorylation), and increased hemoglobin production, indicating differentiation.
Conclusions:
- An OR-mediated pathway regulating proliferation, apoptosis, and differentiation in CML and AML was identified for the first time.
- This pathway, particularly involving OR2AT4, presents novel therapeutic targets for AML treatment.
