Similarities of the Erythrocytes in Juvenile Chronic Myelogenous Leukemia to Fetal Erythrocytes

A 4-yr-old boy was studied who showed typical findings of juvenile chronic myelogenous leukemia, including massive hepatosplenomegaly, thrombocytopenia, low leukocyte alkaline phosphatase, and absence of a Philadelphia chromosome. The erythrocytes of the patient exhibited many characteristic features of erythrocytes of newborn infants: the fetal hemoglobin concentration was greatly elevated (72%); the oxygen dissociation curve of the whole blood was displaced to the left of the curve from normal adult blood; the hemoglobin A2 level and the erythrocyte I antigen titer were reduced; and a structural analysis of the γ-chain of the fetal hemoglobin showed the glycine to alanine ratio in γ-136 to be typical of the neonatal pattern. These findings support the suggestion that juvenile chronic myelogenous leukemia is accompanied by reversion to a fetal pattern of erythropoiesis.

RED CELL METABOLISM IN THE NEWBORN INFANT. IV. TRANSMEMBRANE POTASSIUM FLUX

Measurements of transmembrane potassium flux in the erythrocytes of newborn infants and normal adults demonstrated an increased net loss of potassium in the infants. This loss appeared to be a consequence of decreased active potassium influx rather than an increased membrane permeability. These studies suggest that the erythrocytes of newborn infants may be more vulnerable to destruction resulting from membrane injury because of their reduced capacity for active transport.

GALACTOSE METABOLISM IN THE NEWBORN INFANT

A marked increase was noted in the production of labeled carbon dioxide from galactose-1-C14, and a lesser increase from glucose-1-C14, by erythrocytes of newborn infants as compared to those of adults. It is considered that the increased metabolic activity reflects a greater capability of erythrocytes of newborns to phosphorylate the particular sugars. Estimates were made of galactose-1-phosphate uridyl transferase and galactokinase activities of intact erythrocytes by incubation with galactose-1-C14. Intracellular transferase activity, as measured by the ratio of labeled galactose-1-phosphate to labeled uridine diphosphate galactose, correlated with hemolysate measurements, but the amount of labeled nucleotide alone did not. Intracellular galactokinase activity correlated with hemolysate values provided that galactokinase activity was considered to be represented by the sum of the galactose-1-phosphate and nucleotide produced during incubation with galactose. The rate of removal of galactose from the blood of newborns after intravenous administration was slower than with adults. However, the rate of disappearance cannot be considered to reflect galactose utilization until more is known concerning regulatory factors in the newborn infant.

Hydrogen Peroxide Toxicity and Detoxification in the Erythrocytes of Newborn Infants

The deleterious effects on erythrocytes of low steady-state concentrations of H2O2 in vitro have been compared in samples from full-term and premature infants and adults. Methemoglobin and Heinz bodies were formed to a greater degree in the intact erythrocytes of the young subjects. In the absence of protective enzymes, however, the extent of oxidation was similar in hemoglobin prepared from cord blood and from adult blood, respectively. Activity of the enzymes involved in the detoxification of H2O2 has been measured in the red blood cells of the aforementioned groups of subjects. Of note was the finding of significantly decreased activity of glutathione peroxidase in the full-term newborn and premature infants. These findings of increased toxicity from H2O2 and decreased efficiency of the detoxification mechanisms are considered to have bearing on the susceptibility of young subjects to drug-induced hemolytic anemia.