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Cobalamin‐dependent metabolism in chronic myelogenous leukemia determined by deoxyuridine suppression test and the formiminoglutamic acid and methylmalonate excretion in urine
Author(s) -
Gimsing Peter,
Hippe Erik
Publication year - 1995
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.2830490205
Subject(s) - cobalamin , urine , excretion , chronic myelogenous leukemia , medicine , leukemia , deoxyuridine , metabolism , endocrinology , chemistry , biochemistry , vitamin b12 , dna
The cobalamin metabolism in chronic myelogenous leukemia (CML) was evaluated in 18 newly diagnosed and untreated patients by formiminoglutamic acid (FiGlu) and methyl malonic acid excretion (MMA) tests. A deoxyuridine (dU) suppression test of bone marrow cells was compared in patients 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 folate deficiency (N = 22). All had normal MMA excretion but 3 of 15 patients had increased FiGlu excretion. In vitro thymidine uptake in bone marrow cells of CML patients were lower (mean 40 fmol/106 cells) than pernicious anemia patients (115 fmol/106 cells). Methotrexate (MTX) increased the uptake in all cases. Addition of formyl‐THF, methyltetrahydrofolate (methyl‐THF), and pteroylglutamic acid (PGA) tended to normalize the effect of MTX. In pernicious anemia methyl‐THF only decreased the uptake in combination with CN‐Cbl. dU suppression values were significantly higher (6.3%) in CML than in the reference group (4.4%), but significantly lower than in pernicious anemia (41.6%) and folate deficiency (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 significantly in all patients, but more in CML (64.5%) than in pernicious anemia (48.6%) and controls (49.8%). The MTX effect was to some extent neutralized by folate analogues with formyl‐THF as the most effective followed by methyl‐THF and lastly PGA. Methyl‐THF also neutralized MTX in pernicious anemia, but its effect was certainly enhanced by addition of CN‐Cbl. Thymidine uptake and dU suppression patterns were not significantly changed in CML after treatment with busulfan for 1 week or in accelerated phase. We concluded that signs of cobalamin or folate deficiency (apart from one patient) cannot be demonstrated in untreated CML. However, dU suppression was significantly increased and more so in circulating myeloid cells than in bone marrow. This indicates a deranged metabolism of deoxynucleotides which is independent of cobalamin and folates, and a difference between bone marrow cells and circulating cells. dU suppression is a valuable indicator of cobalamin deficiency. Preincubation with MTX may assist the diagnosis by demonstrating methyl‐THF‐neutralized thymidine up‐take and dU suppression in combination with CN‐Cbl in patients with pernicious anemia. However, further clinical studies are needed to tell whether the extension of the test is justified by giving additional clinical information. © 1995 Wiley‐Liss, Inc.