Human cyclic hematopoiesis is associated with aberrant purine metabolism.
It appeared possible that abnormal purine or pyrimidine metabolism could cause cyclic hematopoiesis by analogy with the defective lymphopoiesis associated with inherited deficiencies of adenosine deaminase and purine nucleoside phosphorylase. Therefore, we examined erythrocyte purine and pyrimidine nucleotide levels, as well as plasma purine and pyrimidine nucleosides and bases in three patients and in normal controls. These studies showed that during neutropenia there was a significant elevation in the levels of guanosine triphosphate (P = 0.005) and adenosine triphosphate (P less than 0.001) in the patients' red cells not attributable to reticulocyte variation. Serial analysis of a patient's plasma showed a fivefold elevation of hypoxanthine (10.6 mumol/L) during neutropenia, with a return to normal values (1.4 mumol/L) as neutrophil numbers increased. Plasma inosine was also significantly elevated in comparison with normal control values (2.0 mumol/L vs. 0.8 mumol/L), whereas plasma and urinary uric acid were within the normal range. Serial analysis of red cells and plasma from two patients with chronic neutropenia showed no elevations of purine or pyrimidine metabolites. These results provide evidence of a link between abnormal concentrations of purine metabolites and cyclic hematopoiesis, and permit the speculation that aberrant purine metabolism is primarily related to the defective hematopoietic cell proliferation that is characteristic of this disease.
D000243:Adenosine Deaminase / Q000097:blood; D000328:Adult; D000380:Agranulocytosis / Q000097:blood*; D002648:Child; D002851:Chromatography, High Pressure Liquid; D002908:Chronic Disease; D005260:Female; D006160:Guanosine Triphosphate / Q000097:blood; D006400:Hematocrit; D006410:Hematopoiesis; D006801:Humans; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000097:blood / Q000652:urine; D007288:Inosine / Q000097:blood / Q000652:urine; D008297:Male; D009503:Neutropenia / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D009705:Nucleosides / Q000097:blood / Q000652:urine; D009711:Nucleotides / Q000097:blood / Q000652:urine; D011687:Purines / Q000097:blood*; D011743:Pyrimidines / Q000097:blood*; D014527:Uric Acid / Q000097:blood / Q000652:urine
D007042:Hypoxanthines; D009705:Nucleosides; D009711:Nucleotides; D011687:Purines; D011743:Pyrimidines; D014527:Uric Acid; D019271:Hypoxanthine; D007288:Inosine; D006160:Guanosine Triphosphate; D000243:Adenosine Deaminase