Ultrastructure and cytokinetics of leukemic myeloblasts containing giant granules

Leukemic myeloblasts containing abnormal granules were studied with ultrastructural, cytochemical, and thymidine labeling techniques to evaluate defects in granulogenesis and proliferation. Giant granules (1 to 3 micron in diameter) and Auer rods were observed in leukemic cells from two patients, and only rarely were both abnormal granule types observed in the same cell. The lysosomal origin of these abnormal granules was demonstrated by their content of peroxidase, esterase, and anionic glycoconjugates. Fusion of small dense granules (less than 0.2 micron in diameter) appeared to be increased in cells containing Auer rods and/or giant granules, but fusion of intact primary granules (0.2 to 0.4 micron in diameter) and sequestration of cytoplasmic contents were observed only in giant granules and not in Auer rods. Although the small granules that fused to form giant granules and Auer rods appeared similar, there was no evidence for transformation of giant granules into Auer rods. In one patient, cells with abnormal granules could easily be distinguished from the larger population of cells that lacked abnormal granules. The perturbation of these two distinct populations by chemotherapy was evaluated with thymidine labeling experiments. A high percentage (2- or 3-fold greater) of the abnormally granulated myeloblasts incorporated tritiated thymidine when compared to myeloblasts without abnormal granules in the same specimen. This difference could have resulted from an underlying metabolic defect which affected both granulogenesis and cell division. These results demonstrate that the formation of giant granules in leukemic cells is morphologically similar to that observed in the Chediak-Higashi syndrome and that leukemic cells with abnormal granules may differ cytokinetically from uninvolved leukemic cells.