Purine metabolism in relation to leukemia and lymphoid cell differentiation

A number of inborn errors of purine metabolism have been associated with immunodeficiency diseases. From studies to the possible mechanism(s) leading to the defects in the immune system, it appeared that the accumulation of deoxyATP and deoxyGTP and the subsequent inhibition of ribonucleotide reductase played an important role. The inhibition of methylation pathways through the accumulation of s-adenosylmethionine seems to be a second valid concept. The amount to which certain subtypes of lymphoid cells were affected by the enzyme deficiencies was strongly related to the enzymatic make-up of the cells. Lymphoid cells from different maturation stages could be affected in a specific way, depending on the different enzyme activities of these cells. Studies on human lymphoblastic leukemias showed that, related to the immunological subtype, the different leukemias could be characterized by a different enzymatic make-up. In this paper we discuss the possibilities for a specific enzyme directed chemotherapy, directed against specific subtypes of human lymphoblastic leukemias. Experimental evidence indicates that for example the adenosine deaminase inhibitor 2'deoxycoformycin can be used as a specific drug against acute lymphoblastic leukemia with the T cell phenotype.