Olfactory Receptor Family 7 Subfamily C Member 1 as a potential prognostic marker for pediatric T‐cell acute lymphoblastic leukemia patients

Abstract

A recent study showed that self‐renewing colorectal cancer‐stem cells/cancer‐initiating cells ectopically express the olfactory receptor family 7 subfamily C member 1 (OR7C1). OR7C1, which is a G protein‐coupled receptor (GPCR) was associated with the expression of stem‐cell markers and decreased survival of colon cancer patients. We study T‐cell acute lymphoblastic leukemia (T‐ALL), a neoplasm of immature T‐cell precursors that predominately affect children with an incidence of ~20% of the overall acute lymphoblastic leukemia (ALL) cases. In a screen of 9 pediatric T‐ALL patients, we identified a single nucleotide polymorphism (SNP) in the OR7C1 gene in isolated T‐cells from all 9 patients with T‐ALL that was not present in control T‐cells. Based on published 3D structures of GPCRs we have used in silico modeling to predict the structural effects of the OR7C1 point mutation located in the second extracellular loop, which we expect will regulate downstream signaling. We hypothesize that the SNP form of OR7C1 contributes to the proliferation and aggressiveness of T‐ALL. We identified OR7C1 expression in human T‐ALL cell lines by reverse transcription PCR and western blot analysis with no expression in control peripheral blood mononuclear cells. Sequencing of amplified DNA from T‐ALL cell lines determined the same OR7C1 SNP in two of the human T‐ALL cell lines that we observed in pediatric T‐ALL patients. Using an antibody to OR7C1, we have isolated OR7C1 expressing cells by fluorescence‐activated cell sorting in T‐ALL cell line, HuT78. Currently, we are determining the stemness characteristics of our enriched OR7C1 expressing HuT78 population with the aim of defining the role of OR7C1 in T‐ALL cell proliferation and invasiveness.Support or Funding InformationResearch reported in this poster was supported by the National Institute of General Medical Sciences of the National Institutes of Health under linked Award Numbers SC1GM111172, RL5GM118969, TL4GM118971, UL1GM118970, and 5G12MD007592.The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.