Blood, 1973, Vol. 41, No. 4, pp. 497-504.
© 1973 American Society of Hematology, Inc.
Biochemical Abnormality of DNA Synthesis of
Erythroblasts in Acute and Chronic Myeloid Leukemia
Peter Ernst 1,
Michele Baccarani 1, and
Sven-Aage Killmann 1
1 Division of Hematology, Department of Medicine A, Rigshospitalet, University
Hospital of Copenhagen, Copenhagen, Denmark.
Six patients with acute and chronic myeloid
leukemia (AML and CML) showed a low
incorporation of labeled DNA precursors
into basophilic erythroblasts. Based on
mitotic indices and the use of vincristine
as a stathmokinetic tool, it was evident that
brisk proliferation in this cell compartment
took place. Microspectrophotometric determination of single-cell DNA content
showed that a considerable fraction of the
erythroid cells were in DNA synthesis without incorporating an exogeneously supplied DNA precursor. Following inhibition
of the de novo synthesis of nucleoside triphosphates, the cells showed capacity for
precursor incorporation. It is suggested
that a biochemical abnormality, which
leads to a high intranuclear nucleoside
triphosphate pool, may inhibit nucleoside
kinases and hence the utilization of labeled nucleosides, as well as diluting the
labeled precursors. The defect should
probably be considered to be a biochemical expression of "leukemicness" of the
erythroid cells. The frequency of the phenomenon described here cannot be determined from the present study. The patients
are part of a series of 44 patients who were
studied with the purpose to investigate the
effect of cytostatic treatment on the cell
cycle of the leukemic cells. Many of the
patients had so little erythropoiesis left
that studies as those described here could
not be carried out. Therefore, the reported
frequency of 6/44 of the observed phenomenon is almost certainly an underestimate.
Consequently, cytokinetic studies of erythropoiesis in CML and AML, using tracer
techniques alone, must be evaluated with
caution.
Submitted on July 10, 1972
Revised on August 21, 1972
Accepted on August 23, 1972
