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)
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 proteincoupled 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.
Molecular biology|Cellular biology|Public health
Lozano, Eduardo Elias Chaib, "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). ETD Collection for University of Texas, El Paso. AAI29210186.