inosinic-acid and Leukemia--Lymphocytic--Chronic--B-Cell

Topics: Adenosine Monophosphate; Aged; Humans; Inosine Monophosphate; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphocytes; Middle Aged; NAD; Purine Nucleotides

The synthesis of purine nucleotides has been studied in human peripheral blood lymphocytes from healthy subjects and patients affected by B-cell chronic lymphocytic leukemia (B-CLL). The rate of the synthesis was measured by following the incorporation of 14C-formate into the nucleotides of lymphocyte suspensions. The whole sequence AMP-->ADP-->ATP was found reduced in B-CLL lymphocytes; in the case of guanylates only the last step of the sequence GMP-->GDP-->GTP was significantly lower in the same cells. From the analysis of these results, combined with previous data, we conclude that purine metabolism undergoes an imbalancement during CLL, which is partially compensated, and point out the importance of studying concomitantly purine metabolism and nucleic acid synthesis in leukemia cells.

Topics: Adenine Nucleotides; Adenosine Monophosphate; Aged; Carbon Radioisotopes; Cells, Cultured; Guanine Nucleotides; Guanosine Monophosphate; Humans; Inosine Monophosphate; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphocytes; Middle Aged; Time Factors

The metabolism of purine nucleotides was studied in human peripheral blood lymphocytes from healthy subjects and patients with B-cell chronic lymphocytic leukemia. Nucleotide content was determined by HPLC. The rate of de novo synthesis of purine nucleotides was measured kinetically by following the incorporation of 14C-formate into the nucleotides of a lymphocyte suspension. The patterns of the main enzymes involved in purine nucleotide metabolism (those of the salvage pathway and catabolism) were estimated by a radiochemical method. Although the data expressed in relation to cells and protein showed some discrepancies, several common differences were evident in both cases. The main differences were an increase in NAD and IMP, a sharp decrease in 5'-nucleotidase activities and in total guanylate content and synthesis, and an increase in the A/G ratio in lymphocytes of patients with respect to controls. The changes in these parameters in CLL indicate an imbalance in purine metabolism and may play a specific role in the biology of the leukemia cell. They are also potential biochemical markers of lymphoid malignancies and may be useful in chemotherapic applications.

Topics: 5'-Nucleotidase; Adenine Nucleotides; Adenine Phosphoribosyltransferase; Aged; Chromatography, High Pressure Liquid; Humans; Hypoxanthine Phosphoribosyltransferase; Inosine Monophosphate; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphocytes; Middle Aged; NAD; Purine Nucleotides

Topics: 5'-Nucleotidase; Adenosine Monophosphate; B-Lymphocytes; Cytosol; Humans; Inosine Monophosphate; Isoenzymes; Leukemia, Lymphocytic, Chronic, B-Cell; Reference Values; Substrate Specificity; T-Lymphocytes

Topics: Adenine Nucleotides; Aged; Aged, 80 and over; Cell Survival; Chromatography, High Pressure Liquid; Female; Guanine Nucleotides; Humans; Inosine Monophosphate; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Leukocytes; Male; Middle Aged; NAD; Neutrophils; Purine Nucleotides; Reference Values

Topics: Adenine Nucleotides; Guanine Nucleotides; Humans; Inosine Monophosphate; Leukemia, Lymphocytic, Chronic, B-Cell; Leukocytes; Leukocytes, Mononuclear; NAD; Neutrophils; Purine Nucleotides; Reference Values

At the "inosinic branch point", inosinic acid (IMP) can be channelled either to guanylic acid (GMP) or to adenylic acid (AMP). The 4 enzymes involved in these processes are IMP-dehydrogenase (IMP-DH) and GMP synthetase for the formation of GMP and adenylosuccinate (AMP-S) synthetase and lyase for the formation of AMP. The Authors study the behavior of these enzymes in peripheral blood lymphocytes from normal and leukemic patients. The cells were isolated as previously reported. GMP synthetase was assayed with radiochemical method, IMP-DH and AMP-S synthetase with a radiochemical method coupled to HPLC, while AMP-S lyase was determined following the formation of AMP separated by AMP-S by HPLC, without using labelled precursors. Except for GMP synthetase, which was very low, no activity was detectable in normal lymphocytes; while AMP-S was absent also in leukemic cells, the remaining three activities were well evident. The results open the possibility of using the inosinic branch point enzymes as tumor markers.

Topics: Adenylosuccinate Lyase; Adenylosuccinate Synthase; Carbon-Nitrogen Ligases; Humans; IMP Dehydrogenase; Inosine Monophosphate; Inosine Nucleotides; Leukemia, Lymphocytic, Chronic, B-Cell; Ligases; Lymphocytes