Biochemical consequences of 2′-deoxycoformycin treatment in a patient with T-cell lymphoma. Some unusual findings

Abstract

The nucleotide content of the various blood cells and the urinary excretion of purine and pyrimidine metabolites were studied in a patient with a T-cell lymphoma (early T-cell phenotype) before and during treatment with deoxycoformycin (dCF; given intravenously [iv] during 3 days, biweekly). During and after the administration of dCF, high amounts of dATP were found in the lymphoid cells and the erythrocytes (maximally, 480 pmol/106 lymphocytes and 5.5 nmol/106 erythrocytes), but not in the polymorphonuclear leukocytes. The amount of dATP in the erythrocytes, however, was significantly lower than described in the literature. During each administration of dCF, the number of blast cells in the peripheral blood rose initially, followed by a rapid decrease. After three courses, a hematologic remission was achieved and maintained for 6 weeks; then an autologous bone-marrow transplantation was performed. During the first dCF course a large amount of deoxyadenosine was found in the urine. During the second course, this excretion was much lower, but still higher than in healthy individuals. In the patient described, dCF showed a highly specific toxicity for the immature T-lymphoblast; hardly any changes were seen in the numbers of the other hematopoietic cells, both in the blood and in the bone marrow.

The effect of increasing nucleotide-sugar concentrations on the incorporation of sugars into glycoconjugates in rat hepatocytes

“…Although we could not discriminate between N-acetylglucosamine and N-acetylgalactosamine, this observation may have to be interpreted as an enhanced capacity for formation of branched N-linked glycans and of polylactosaminoglycan chains. Interestingly such an enhancement has been associated with malignant transformation of cells (Hubbard, 1987;De Korte et al, 1987;Van den Eijnden et al, 1988;Easton et al, 1991Easton et al, , 1992. The latter process in malignant cells, however, is generally accompanied by an intreased sialylation, whereas here sialylation is depressed.…”

Mechanism and control of degradation and resynthesis of adenylates in tumour cells

“…We therefore assume that instability or imbalance of the pool could be one of the essential features of energy metabolism of malignant cells. For that reason the problem of instability of concentration of adenylates in cancer cells deserves greater attention, although it has been the subject of numerous investigations [6][7][8][9][10][11]. We reported recently [12] that the operation of the purine nucleotide cycle is an important mechanism for regeneration of the pool of adenine nucleotides in Ehrlich ascites carcinoma (EAC) cells on reoxygenation.…”