Regulation Of C-C Chemokine Receptor 7 (CCR7) Ligand-Mediated Internalization And Chemotaxis By G Protein-Coupled Receptor Kinase Family 4 (GRK-4, 5, 6) In Human Pediatric T-Cell Acute Lymphoblastic Leukemia (T-All)
Date of Award
Charlotte M. Vines
Background and Significance: The Hispanic population is disproportionally affected by T-ALL (T-cell acute lymphoblastic leukemia) when compared to other races in the US. C-C Chemokine Receptor 7 (CCR7) in T-ALL is used during disease progression, and may lead to migration of cancerous cells into the Central Nervous System (CNS) of patients. Goals and Objectives: This project aims to find relevant rates and risk factors for T-ALL for the Hispanic population in the US/Mexico border region. The other aim is to assess the effect of the G protein-coupled Receptor Kinase 4 (GRK-4) family proteins on migration and receptor internalization through CCR7 in T-ALL. Hypothesis: The inactivation of the GRK-4 family genes (specifically GRK-5 and -6) in cancerous cells (CEM and Hut-78) will produce a reduction in CCR7-directed migration of these T-ALL cells towards the CCR7 ligands CCL19 and/or CCL21. Methods: Local, state, and national health data agencies were queried for relevant rates of, and data about T-ALL in Hispanics living in the US/Mexico border region. GRK-5, and -6 genes were individually targeted using CRISPR-Cas9 in T-ALL cells to inhibit protein expression. Results: Data about T-ALL in the border region and the city of El Paso is scarce and has discrepancies among different agencies. Leukemias are the most common cancers in children 0 to 20 years of age, and the Hispanic population is more heavily affected than the non-Hispanic White population according to some sources. The expression of GRKs was not reduced with the CRISPR lentivirus approach, but it was somewhat reduced through esiRNA nucleofection. Conclusions: T-ALL is tied to several environmental factors and living conditions that apply to the Hispanic population in the US/Mexico region. Preventing the incidence of this disease requires health awareness interventions and safety regulations in industries where workers are exposed to, or handle leukemogens. The CRISPR-Cas9 experimental results showed no reduction in the expression of GRK-5 or -6, but GRK-6 was partially reduced after esiRNA nucleofection, which could provide an alternative to test the chemotactic and internalization properties of cells once these kinases are inhibited.
Recieved from ProQuest
Eduardo Elias Chaib
Chaib, Eduardo Elias, "Regulation Of C-C Chemokine Receptor 7 (CCR7) Ligand-Mediated Internalization And Chemotaxis By G Protein-Coupled Receptor Kinase Family 4 (GRK-4, 5, 6) In Human Pediatric T-Cell Acute Lymphoblastic Leukemia (T-All)" (2022). Open Access Theses & Dissertations. 3480.