Browsing by Subject "ALL"
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Item ALTERED EXPRESSION OF IMMUNE RECEPTORS 2B4, CS1 AND LLT1 IN CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKEMIA (ALL)(2013-04-12) Tan, CharissePurpose: 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.Item Expression and Function of Immune Receptors in Pediatric Acute Lymphoblastic Leukemia(2016-12-01) Powers, Sheila B.; Stephen O. Mathew; Porunelloor A. Mathew; W. Paul BowmanAcute lymphoblastic leukemia (ALL) is a cancer that mainly affects children around the age of five. Due to current treatments, 80-90% of children achieve long-term remission. However, because of the current treatments, which include chemotherapy and CNS-directed radiation, these children may experience late effects which impact growth and development. Even though survival rate is high, quality of life can be greatly reduced for some of the survivors. Natural Killer (NK) cells are cells of the innate immune system that are important in fighting cancer and virally-infected cells. They have been a subject of interest in ALL because ALL of the B cell lineage is particularly resistant to NK cell killing. NK cells get activated by their surface receptors and their ligands on target cells. In B cell ALL, the NK cells do not appear to get the proper activating signals and this has been determined to be one reason this cancer is able to thrive. Our lab has cloned three immune receptors, 2B4 (CD244), CS1 (CRACC, CD319) and LLT1 (CLEC2D), that are expressed on NK cells as well as other immune cells. These receptors have been shown to play an important role in NK cell activation. Two other receptors, NKp30 and NKp46, are well-known activating receptors that have also been implicated in ALL. In this project I compared the mRNA and surface protein receptor expression of immune receptors between healthy subjects and ALL subjects. Altered expression of immune receptors was observed in ALL subjects. In particular, a significant decrease in mRNA expression of 2B4, LLT1 and NKp30 was observed in ALL subjects at diagnosis compared to healthy subjects. mRNA expression of CS1 was increased significantly after chemotherapy treatment. In contrast, NKp46 mRNA expression was significantly increased in ALL subjects as compared to healthy subjects. Cell surface protein expression of CS1 was significantly upregulated on T cells and monocytes and LLT1 on NK cells of ALL subjects at diagnosis. Interestingly, NKp30 was overexpressed on B cells, T cells, monocytes and NKp46 was overexpressed on T cells and monocytes but not on NK cells of ALL subjects at diagnosis. I also detected a significant increase of soluble CS1and BAT-3 in ALL subjects at diagnosis between the ages of 1-11 yrs. Also, soluble CD48 was significantly increased in ALL subjects after chemotherapy treatments. Future mechanistic studies may shed more light in the immune dysfunction in ALL ultimately contributing to better treatment options for patients with pediatric ALL.