ALTERED EXPRESSION OF IMMUNE RECEPTORS 2B4, CS1 AND LLT1 IN CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKEMIA (ALL)

Purpose: Acute lymphoblastic leukemia is the most common type of leukemia found in children with peak prevalence between the ages of 2 and 5. In ALL, there is uncontrolled, exaggerated growth and accumulation of lymphoid progenitor cells, which fail to properly differentiate and function as normal lymphocytes. Despite current treatment protocols that have been successful in the vast majority of ALL patients, serious acute and late complications are frequent and resistance to chemotherapy often develops. Natural Killer (NK) cells, which are components of the lymphocyte population, can recognize and act on target cells under the control of their cell surface receptors. Binding of these receptors to specific ligands on the target cell results in signaling which either activates or inhibits NK cell effector functions. We have previously identified cell surface receptors 2B4, CS1 and LLT1 playing a major role in NK cell activation. Previous studies on these receptors implicate that these receptors may play a role in cancers, however their significance and role in childhood ALL have not been evaluated. We hypothesize that altered expression of these immune receptors play a role in acute lymphoblastic leukemia in children. Methods: 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. Peripheral blood mononuclear cells (PBMC) were isolated from whole blood of twelve ALL subjects and three healthy subjects. NK92-MI cell line was used as a positive control. Total RNA was extracted and reverse transcribed (RT-PCR) into complimentary DNA (cDNA). PCR was performed using primers specific to 2B4, CS1, LLT1, and expression was normalized to β-actin. Results: ALL subjects showed altered expression of 2B4 in PBMC as compared to healthy subjects. There was an overall decrease in the expression of CS1 receptor in ALL subjects as compared to healthy subjects. Interestingly, both ALL and healthy subjects showed expression of different isoforms of the LLT1 receptor with variations in their expression level. Conclusions: Results implicate that there are alterations in the expression of immune receptors that may mediate the immune dysregulation in ALL subjects. Expression and functional analysis of these receptors in a larger population of ALL subjects will provide vital knowledge furthering our understanding of the etiology of ALL, progression, and developing potential immunotherapies.