Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults, with a 5-year overall survival rate of approximately 30%. Despite recent advances in therapeutic options, relapse remains the leading cause of death and poor survival outcomes. New drugs benefit specific small subgroups of patients with actionable therapeutic targets. Thus, finding new targets with greater applicability should be pursued. Olfactory receptors (ORs) are seven transmembrane G-protein coupled receptors preferentially expressed in sensory neurons with a critical role in recognizing odorant molecules. Recent studies have revealed ectopic expression and putative function of ORs in nonolfactory tissues and pathologies, including AML. Here, we investigated OR expression in 151 AML samples, 6400 samples of 15 other cancer types, and 11,200 samples of 51 types of healthy tissues. First, we identified 19 ORs with a distinct and major expression pattern in AML, which were experimentally validated by RT-PCR in an independent set of 13 AML samples, 13 healthy donors, and 8 leukemia cell lines. We also identified an OR signature with prognostic potential for AML patients. Finally, we found cancer-related genes coexpressed with the ORs in the AML samples. In summary, we conducted an extensive study to identify ORs that can be used as novel biomarkers for the diagnosis of AML and as potential drug targets.

Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults. Although new drugs for specific molecular subsets of AML have recently emerged, the 5-year overall survival rate is still approximately 25%. The treatment options for AML have remained stagnant for decades, and novel molecular targets for this disease are needed. Olfactory receptors (ORs) are seven transmembrane G-protein coupled receptors preferentially expressed in sensory neurons, in which they play a critical role in recognizing odorant molecules. Recent studies have revealed ectopic expression and putative function of ORs in nonolfactory tissues and pathologies, including AML. Here, we comprehensively investigated OR expression in 151 AML samples, 51 healthy tissues (approximately 11,200 samples), and 15 other cancer types (6,400 samples). Our analyses identified a group of 19 ORs with a distinct and major expression pattern in AML. The expression of these ORs was experimentally validated in an independent set of AML samples and cell lines. We also identified an OR signature with prognostic value for AML patients. Finally, we identified cancer-related genes that were coexpressed with the ORs in the AML samples. In summary, we conducted a high-throughput computational study to identify ORs that can be used as novel biomarkers for the diagnosis of AML and as potential drug targets. The same approach may be used to investigate OR expression in other types of cancer.