Role of NK Cell Receptors in Acute Lymphoblastic Leukemia in Children

Tan, Charisse S., Role of NK Cell Receptors in Acute Lymphoblastic Leukemia in Children. Master of Science (Biomedical Sciences), May, 2013, 94 pp., 6 tables, 57 illustrations, bibliography, 35 titles. Due to the many medical advances in recent years, treatment of acute lymphoblastic leukemia (ALL) has improved tremendously. It has been estimated that about 80% of children that are diagnosed with this disease will likely go into remission. However, there is still a need for a more specific, less invasive treatment that lessens any toxic side effects of current cancer treatments and at the same time, lowers the risk of relapse. 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 (CD244), CS1 (CRACC) and LLT1 playing a major role in NK cell activation. Along with receptors NKp30 and NKp46, previous studies have shown that these receptors play a role in leukemia and other cancers, however their significance and role in childhood ALL have not been evaluated. Based on this knowledge, this thesis tested the hypothesis that altered expression of these immune receptors may play a role in acute lymphoblastic leukemia in children. The results presented in this thesis demonstrate that there is indeed an alteration in the expression of receptors 2B4, CS1, LLT1, NKp30 and NKp46 in both the mRNA and surface protein level. This data can contribute to further understanding the functional role of these receptors that in turn can help develop a better mode of treatment for patients with childhood ALL.