Uridine kinase activities in normal and neoplastic lymphoid cells

Area of Science:

• Biochemistry
• Cell Biology
• Immunology

Background:

• Uridine kinase (UK) is an enzyme involved in nucleotide metabolism.
• Two forms, adult (Species I) and embryonic (Species II), have been identified.
• Understanding UK activity in lymphocytes is important for cancer research.

Purpose of the Study:

• To investigate the presence and activity of uridine kinase (UK) in various lymphoid cells, including tumor cells and normal lymphocytes.
• To determine if UK activity correlates with lymphocyte activation or malignancy.
• To explore the effect of 5-azacytidine on UK activity in leukemia cells.

Main Methods:

• Enzyme assays were performed to measure uridine kinase activity.
• Different cell types were analyzed, including transplantable mouse leukemia (EL-4, P815Y), primary tumor cells (feline lymphosarcoma, human leukemias), and normal lymphocytes (calf thymocytes, porcine peripheral blood lymphocytes).
• Phytohemagglutinin was used to stimulate normal lymphocytes, and 5-azacytidine was used to treat tumor cells.

Main Results:

• Both Species I and II uridine kinase (UK) were found in EL-4 leukemia and P815Y mastocytoma cells.
• Only Species I UK was detected in primary tumor cells and normal lymphocytes.
• Species I UK activity was significantly induced (4-fold) in phytohemagglutinin-stimulated normal lymphocytes.
• UK activity in feline lymphosarcoma and childhood lymphocytic leukemia was similar to induced normal lymphocytes.
• Lymphocytes from a patient with chronic lymphocytic leukemia of thymus-independent origin showed UK activity comparable to unstimulated cells.
• 5-azacytidine treatment repressed UK activity in EL-4 tumor cells.

Conclusions:

• Uridine kinase (UK) activity, particularly Species I, is associated with proliferating and activated lymphocytes.
• The presence of Species I UK in lymphoid tumors suggests its involvement in lymphocyte malignancy.
• UK activity levels may serve as a biomarker for distinguishing between different types of lymphocytic leukemia.
• Pharmacological agents like 5-azacytidine can modulate UK activity in cancer cells.