COBALAMIN-DEPENDENT METABOLISM IN CHRONIC MYELOGENOUS LEUKEMIA DETERMINED BY DEOXYURIDINE SUPPRESSION TEST AND THE FORMIMINOGLUTAMIC ACID AND METHYLMALONATE EXCRETION IN URINE

The cobalamin metabolism in chronic myelogenous leukemia (CML) was eva luated in 18 newly diagnosed and untreated patients by formiminoglutam ic acid (FiGlu) and methyl malonic acid excretion (MMA) tests. A deoxy uridine (dU) suppression test of bone marrow cells was compared in pat ients with acute myelogenous leukemia (N = 5), myelodysplastic disease (N = 3), untreated pernicious anemia (N = 16), folate deficiency (N = 7), and a hospital reference group without signs of cobalamin or fola te deficiency (N = 22). All had normal MMA excretion but 3 of 15 patie nts had increased FiGlu excretion. ln vitro thymidine uptake in bone m arrow cells of CML patients were lower (mean 40 fmol/106 cells) than p ernicious anemia patients (115 fmol/106 cells). Methotrexate (MTX) inc reased the uptake in all cases. Addition of formyl-THf, methyltetrahyd rofolate (methyl-THF), and pteroylglutamic acid (PGA) tended to normal ize the effect of MTX. In pernicious anemia methyl-THF only decreased the uptake in combination with CN-Cbl. du suppression values were sign ificantly higher (6.3%) in CML than in the reference group (4.4%), but significantly lower than in pernicious anemia (41.6%) and folate defi ciency (28.5%). The dU suppression values in bone marrow cells of CML patients correlated significantly with the transferrin saturation. In buffy coat cells du suppression values were even higher (9.3%) than in bone marrow cells of the same CML patients. Addition of folate forms and CN-Cbl did not change the dU suppression values in CML, as it did in pernicious anemia. MTX increased dU suppression values significantl y in all patients, but more in CML (64.5%) than in pernicious anemia ( 48.6%) and controls (49.8%). The MIX effect was to some extent neutral ized by folate analogues with formyl-THF as the most effective followe d by methyl-THF and lastly PGA. Methyl-THF also neutralized MTX in per nicious anemia, but its effect was certainly enhanced by addition of C N-Cbl. Thymidine uptake and dU suppression patterns were not significa ntly changed in CML after treatment with busulfan for 1 week or in acc elerated phase. We concluded that signs of cobalamin or folate deficie ncy (apart from one patient) cannot be demonstrated in untreated CML. However, dU suppression was significantly increased and more so in cir culating myeloid cells than in bone marrow. This indicates a deranged metabolism of deoxynucleotides which is independent of cobalamin and f olates, and a difference between bone marrow cells and circulating cel ls. dU suppression is a valuable indicator of cobalamin deficiency. Pr eincubation with MTX may assist the diagnosis by demonstrating methyl- THF-neutralized thymidine uptake and dU suppression in combination wit h CN-Cbl in patients with pernicious anemia. However, further clinical studies are needed to tell whether the extension of the test is justi fied by giving additional clinical information. (C) 1995 Wiley-Liss, I nc.