Leucocyte Folate in Vitamin B<sub>12</sub> and Folate Deficiency and in Leukaemia

Hoffbrand, A. V.; Newcombe, Beverley F. A.

doi:10.1111/j.1365-2141.1967.tb08866.x

Cited by 29 publications

(7 citation statements)

References 24 publications

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“…The total folate concentrations in leucocytes found here are substantially similar to those reported previously (Swendseid, Bethell & Bird, 1951;Hoffbrand & Newcombe, 1967). The generally higher L. casei activity than S. faecalis activity suggests that, in most cases, methylfolates comprise a major proportion of leucocyte folate but there was no consistent difference in ratio of these two micro- biological activities according to the type of leukaemia or the degree of primitiveness of the cells.…”

Section: Discussionsupporting

confidence: 89%

Polyglutamate Forms of Folate in Resting and Proliferating Mammalian Tissues

et al. 1975

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1. Tritiated folic acid (pteroylglutamic acid) was injected into rats whose livers were undergoing regeneration after partial hepatectomy, and into normal control rats. 2. The major form of labelled liver folate was found to be pteroylpentaglutamate in both hepatectomized and normal rats and there was no difference in the proportion of pteroylpentaglutamate to other forms of folate in the regenerating or resting liver. 3. Folate concentrations were also measured in leucocytes from normal and leukaemic patients. 4. Pteroylpolyglutamates constituted the main form of folate in both sets of cells. There was again no difference in proportion of pteroylpolyglutamate to pteroylmonoglutamate forms of folate between normal mature cells and primitive blast cells. 5. It is therefore suggested that pteroylpolyglutamates, which constitute nearly all the folates in cells actively synthesizing DNA and protein as well as in resting cells, probably act as the coenzymes in vivo for the folate-dependent reactions in DNA, RNA and protein synthesis in mammalian systems.

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Section: Discussionsupporting

confidence: 89%

Polyglutamate Forms of Folate in Resting and Proliferating Mammalian Tissues

et al. 1975

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“…Swendseid et a1 [21] measured leucocyte folate by microbiologic assay, reporting average values of 80 ng/ml of packed cells, and indicated that the leucocytes themselves contained sufficient conjugase to hydrolyze all of their own folate. Hoffbrand and Newcombe [8] confirmed that addition of conjugase to leucocyte suspensions before sonication did not significantly alter the mean microbiologic folate activity of these cells. The leucocyte folate levels in normal subjects were similar to those previously reported (60-123 nglml), but they were subnormal in all patients whose marrow showed giant metamyelocytes or obvious megaloblastic changes.…”

Section: Lymphocyte Dumentioning

confidence: 80%

Abnormal lymphocyte deoxyuridine suppression test: A reliable indicator of decreased lymphocyte folate levels

Colman

Herbert

1980

American J Hematol

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The deoxyuridine (dU) suppression test measures the availability of folate and, indirectly, vitamin B12 in de novo thymidine synthesis and is of established value in defining biochemical megaloblastosis in bone marrow cells. Recent studies have suggested that the application of this test to DNA synthesis in transformed lymphocytes may be valuable in defining nutrient deficiency that is subtle, masked, or present in some cell lines but not in others. This use of the test has not been fully accepted because lymphocyte folate and B12 levels had not been simultaneously measured prior t o the current study. In this study, vitamin availability for the dU suppression test was closely correlated with folate levels in radioassay and less well correlated with vitamin B12 levels in the cell. The folate levels varied widely when dU suppression was efficient but were uniformly low in subjects with ineffective dU suppression. These studies validate the use of the lymphocyte dU suppression test as a means of detecting folate deficiency in this cell line.

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“…Although the precise significance of this localized defect is not yet clear, it suggests that selective nutrient deficiency may occur in one but not another cell line competing for limited available nutrients in the same subject. It should be noted that the concept of a folate deficiency state localized to a particular cell line goes back at least as far as the reports of Newcombe (1966) andLindenbaum et al(1975), which have been summarized by Lindebaum (1977).…”

Section: Discussionmentioning

confidence: 98%

Unmasking Covert Folate Deficiency in Iron‐Deficient Subjects with Neutrophil Hypersegmentation: dU Suppression Tests on Lymphocytes and Bone Marrow

et al. 1978

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Fifteen patients with apparently uncomplicated iron‐deficiency anaemia were studied to determine the presence of covert folate or vitamin B12 deficiency. None had morphologic or conventional biochemical evidence of folate or vitamin B12 deficiency on admission, except for neutrophil hypersegmentation in peripheral blood smears of 10 of the 15 patients, and giant metamyelocytes in some of the bone marrow aspirates. Although deoxyuridine (dU) suppression tests on pretreatment bone marrow were normal in all 15 patients, similar tests on pretreatment transformed lymphocytes were characteristic of folate deficiency in eight of 14 patients (57%), with poor transformation obscuring results in the fifteenth subject. After six patients were given 6 weeks of oral folate and iron therapy, the dU suppression test was repeated in the lymphocytes of two subjects who demonstrated folate deficiency in this test on admission. The test still showed folate deficiency, supporting our prior report that the test was useful as a marker of past folate deficiency despite intervening folate therapy. The nine remaining subjects received iron alone for 3–6 weeks, which produced no change in serum folate, red cell folate, or dU suppression tests in lymphocytes. In five of the nine subjects (56%), however, an abnormality characteristic of folate deficiency appeared for the first time in bone marrow dU suppression tests, with morphologic megaloblastosis developing frankly in four and equivocally in one. Four of these five subjects had a folate corrected defect in the lymphocyte dU suppression test before treatment, and the fifth was the subject in whom lymphocytes did not transform sufficiently to allow testing for the defect. These observations: 1. Suggest that when a patient with apparently uncomplicated iron deficiency has hypersegmentation of his granulocyte nuclei, underlying folate deficiency should be sought. It was found in nine of the 10 current such subjects. 2. Suggest that the most sensitive test to detect covert folate deficiency in contrary to the situation in severe uncomplicated deficiency of vitamin B12 or folate, in which hypersegmentation is striking and rapid scanning of a hundred neutrophils yields a minimum of five with more than five lobes. In uncomplicated iron deficiency, iron binding capacity is almost always elevated above 400 μg/dl. Such levels were seen in only four of our 15 patients, two without hypersegmentation and two with hypersegmentation. This may suggest that a patient population with relatively low total iron binding capacity, perhaps often in association with liver disease, is more likely to have covert folate deficiency with their iron deficiency.

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Leucocyte Folate in Vitamin B₁₂ and Folate Deficiency and in Leukaemia

Cited by 29 publications

References 24 publications

Polyglutamate Forms of Folate in Resting and Proliferating Mammalian Tissues

Polyglutamate Forms of Folate in Resting and Proliferating Mammalian Tissues

Abnormal lymphocyte deoxyuridine suppression test: A reliable indicator of decreased lymphocyte folate levels

Unmasking Covert Folate Deficiency in Iron‐Deficient Subjects with Neutrophil Hypersegmentation: dU Suppression Tests on Lymphocytes and Bone Marrow

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Leucocyte Folate in Vitamin B12 and Folate Deficiency and in Leukaemia

Cited by 29 publications

References 24 publications

Polyglutamate Forms of Folate in Resting and Proliferating Mammalian Tissues

Polyglutamate Forms of Folate in Resting and Proliferating Mammalian Tissues

Abnormal lymphocyte deoxyuridine suppression test: A reliable indicator of decreased lymphocyte folate levels

Unmasking Covert Folate Deficiency in Iron‐Deficient Subjects with Neutrophil Hypersegmentation: dU Suppression Tests on Lymphocytes and Bone Marrow

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Leucocyte Folate in Vitamin B₁₂ and Folate Deficiency and in Leukaemia