Olfactory Receptor Family 7 Subfamily C Member 1 Expression in T‐cell Acute Lymphoblastic leukemia Identifies a Potential Stem Cell Sub‐population

Abstract

Cancer stem cells (CSCs) are thought to be a self‐renewing population that is difficult to kill during standard chemotherapy due to the capacity of the cells for self‐renewal and multidrug resistance. Our lab studies T‐cell acute lymphoblastic leukemia (T‐ALL), which is an aggressive form of leukemia. T‐ALL cells, which can hide from chemotherapeutic treatment regimens within the central nervous system ( CNS), use different chemokine and adhesion receptors to invade the CNS; entry into the CNS contributes to the aggressiveness of the disease. Therefore, migration into the CNS necessitates the use of aggressive treatments such as cranial irradiation and intensified intrathecal chemotherapy, which causes neurocognitive deficits, endocrine disorders, and growth impairment. A recent study showed that the ectopic expression of Olfactory Receptor Family 7 Subfamily C Member 1 (OR7C1) correlates with expression of stem cell markers including SOX2, POU5F1, and LGR5. These stem‐cell markers correlate with decreased survival rates, implicating the expression of these stem cells in chemo‐resistant cancers. Therefore, we hypothesized that the expression of these stem cell markers in T‐ALL cell lines would contribute to the aggressiveness of the disease. Using flow cytometry, we found approximately 1% of HuT78, adult human T‐ALL cells, express OR7C1. Furthermore, while we were able to detect OR7C1 protein expression in HuT78 cells through both Western blot and RT‐PCR, we found that peripheral blood mononuclear cells (PBMCs) lack OR7C1. Currently, we are determining if the expression of OR7C1 leads to the expression of stem cell transcription factors in HuT78, CCRF‐CEM pediatric T cell lines, and PBMCs. These findings will allow us to determine the prognostic significance of OR7C1 in the progression of T‐ALL.Support or Funding InformationNSF award DUE‐1565063This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.