A 62-year-old man and a 73-year-old woman were found to have a nuclear abnormality characterized by exaggerated clumping of the chromatin in the mature granulocytic and erythroid cells. The mature granulocytes showed loss of normal segmentation. The abnormality was not noted in other family members and appeared to be related to an atypical leukemic process. The nuclear abnormality was shown to be associated with a defect in cellular production within the marrow. Granulocyte precursors and normoblasts incorporated 3H-TdR but did not divide. Electron microscopy suggested the distribution of more than normal quantities of heterochromatin to mature leukocytes. Ferrokinetic studies disclosed ineffective erythropoiesis. The sharing of this abnormality by the myeloid and erythroid cells suggests a common stem cell origin.
A functional defect of phagocytosis and cellular aggregation was demonstrated in the neutrophils, but bacterial killing was not affected. The nuclear anomaly described herein may be a pre-leukemic abnormality.
Since this paper was submitted for publication, we have treated two more patients with an identical nuclear defect; an 82-year-old woman and a 79-year-old man. The woman succumbed of acute leukemic transformation, while the man is still alive.