Analysis of expression of immune receptors in pediatric acute lymphoblastic leukemia (ALL)

Acute Lymphoblastic leukemia (ALL) is the most common type of cancer in children. It is characterized by overgrowth of the lymphocyte precursor (either B cell or T cell) that is nonfunctioning, and crowds out other immune cells. Current treatment options have a success rate of 80-90%. However, those who relapse have a survival rate of only around 25-40%. Also, side effects of current chemotherapy and radiation treatments have been shown to impact the normal growth and development of children. Research has shown that ALL of the B cell lineage is particularly resistant to killing by Natural Killer (NK) cells. NK cells are part of the innate immune system and specialize in killing tumor and virally infected cells. NK cell activation is dependent on a balance of inhibitory and activating receptors and their ligands expressed on the target cell. Our laboratory has previously cloned three immune receptors, 2B4, CS1 and LLT1, which have been shown to play a role in cancer, however their significance and role in childhood ALL have not been evaluated. In this study, we evaluated the expression of immune receptors 2B4, CS1, LLT1, NKp30 and NKp46 in pediatric ALL subjects both male and female in the age range of 3 – 18 yrs. ALL subjects and healthy subjects were enrolled at Cook Children’s Hospital and UNT Health Science Center, Fort Worth, TX with informed consent/assent according to IRB approval (UNTHSC IRB# 2008-094 & CCMC IRB# 2008-57). The blood samples were collected and peripheral blood mononuclear cells (PBMC) were isolated and analyzed by flow cytometry and real-time qPCR for expression of immune receptors. ALL subjects showed altered expression of immune receptors in the PBMC as compared to healthy subjects. There was an overall decrease in the expression of 2B4, CS1, LLT1 and NKp46 in the B lymphoblasts of ALL subjects as compared to healthy subjects. Expression and functional analysis of these receptors in a larger sample size will provide valuable insights to conduct future mechanistic studies to investigate the role of these immune receptors in ALL resistance and relapse. Funded by Cancer Research Foundation of North Texas (CRFNT).