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Serum Uracil Levels in Acute Childhood Leukaemia
Author(s) -
Parry T. E.
Publication year - 1978
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1978.tb01094.x
Subject(s) - uracil , white blood cell , cytosine , medicine , gastroenterology , uric acid , endocrinology , chemistry , biochemistry , dna
Serum ‘uracil + uridine’ expressed as uracil has been measured in 47 consecutive cases of acute leukaemia in children at the time of diagnosis, before treatment, and also both before and after therapy in a girl of 12 with Ph 1 positive chronic myeloid leukaemia in blastic transformation, and in an adult male age 31 with acute undifferentiated leukaemia. The results were compared with 97 previously reported normal subjects. The skew distribution of results in acute leukaemia rendered the mean value and standard deviation meaningless but the range was considerably wider than in the normal controls (range 7.2–77.1 μmol/l. in acute leukaemia; mean 15.7 μmol/l., range 5.7–40.5 μmol/l., SD 5.26 in controls). In 10 (21%) of the patients with acute leukaemia the level was more than 3 SDs and in five more than 8 SDs above the normal mean. There was a high degree of correlation between uracil concentration and total white cell count ( r = 0.7894, P <0.001) and blast cell count ( r = 0.7160, P <0.001) but no correlation was observed between serum uracil and the blood urea or the serum uric acid, vitamin B 12 or folate. The grossly elevated uracil levels, white cell and blast cell counts rapidly returned to normal or near normal after therapy. Retention of uracil by the kidney, increased DNA catabolism and the enzymatic deamination of cytosine are considered, and each in turn excluded, as a possible cause of the observed elevated uracil levels. It is submitted that the raised uracil level is a function of the circulating blast cell and that the results are consistent with the hypothesis that, at least in some cases of acute leukaemia, there may be an impairment in the amination of uracil to form cytosine akin to the impaired methylation of deoxyuridylate in the megaloblastic anaemias. The former would enhance the known mutagenic action of uracil, an action which is absent in the latter. The molecular mechanism, whereby this could give rise to a population of genetically abnormal cells incapable of normal differentiation, is discussed.