{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,26]],"date-time":"2023-10-26T13:10:49Z","timestamp":1698325849060},"reference-count":50,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2006,7,11]],"date-time":"2006-07-11T00:00:00Z","timestamp":1152576000000},"content-version":"vor","delay-in-days":4058,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[1995,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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).<\/jats:p><jats:p>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\u2010THF, methyltetrahydrofolate (methyl\u2010THF), and pteroylglutamic acid (PGA) tended to normalize the effect of MTX. In pernicious anemia methyl\u2010THF only decreased the uptake in combination with CN\u2010Cbl. 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\u2010Cbl 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\u2010THF as the most effective followed by methyl\u2010THF and lastly PGA. Methyl\u2010THF also neutralized MTX in pernicious anemia, but its effect was certainly enhanced by addition of CN\u2010Cbl. 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\u2010THF\u2010neutralized thymidine up\u2010take and dU suppression in combination with CN\u2010Cbl 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. \u00a9 1995 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajh.2830490205","type":"journal-article","created":{"date-parts":[[2007,2,21]],"date-time":"2007-02-21T13:54:07Z","timestamp":1172066047000},"page":"121-130","source":"Crossref","is-referenced-by-count":1,"title":["Cobalamin\u2010dependent metabolism in chronic myelogenous leukemia determined by deoxyuridine suppression test and the formiminoglutamic acid and methylmalonate excretion in urine"],"prefix":"10.1002","volume":"49","author":[{"given":"Peter","family":"Gimsing","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erik","family":"Hippe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,7,11]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0145-2126(87)90067-1"},{"key":"e_1_2_1_3_2","first-page":"264","article-title":"The turnover of 57Co\u2010labeled cyanocobalamin bound to cobalamin binding proteins in patients with chronic myelogenous leukemia","volume":"123","author":"Gimsing P","year":"1994","journal-title":"J Lab Clin Med"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)42521-3"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.10.3.258"},{"key":"e_1_2_1_6_2","first-page":"487","article-title":"Pernicious anaemia and myeloid leukaemia. 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