Defective alpha-granule production in megakaryocytes from gray platelet syndrome: ultrastructural studies of bone marrow cells and megakaryocytes growing in culture from blood precursors.

The ultrastructure and cytochemistry of megakaryocytes from two patients with a familial gray platelet syndrome are described. Although the Golgi zones appeared normally developed, the megakaryocytes lacked alpha-granules. Catalase-containing particles were normal in number. In immature megakaryocytes, granules measuring from 0.05-0.1 mu and having an electron-dense core occurred in the Golgi area. These granules, which are considered as the precursors of alpha-granules in normal megakaryocytes, appeared unable to mature, and their number decreased with the megakaryocyte maturation. The presence of dense material in distended demarcation membranes and/or vacuoles suggested that their content was discharged. It is suggested that myelofibrosis present in the bone marrow from these two patients may be related to the possible excretion of a polypeptide growth factor normally contained in the alpha-granules. Megakaryocytes grown by the plasma clot procedure from blood precursors isolated from the two patients also did not exhibit alpha-granules, which were replaced by vacuoles. Our findings suggest that the lack of alpha-granules in gray platelets may be related to a defective megakaryocyte-committed cell, and evidence is presented which suggests that the precursors of alpha-granules are produced but that their contents are then lost.