MYELOFIBROSIS AND ACUTE MEGAKARYOBLASTIC LEUKEMIA IN A CHILD - TOPOGRAPHIC RELATIONSHIP BETWEEN FIBROBLASTS AND MEGAKARYOCYTES WITH AN ALPHA-GRANULE DEFECT

In a child with acute megakaryoblastic leukemia, severe thrombocytopenia and myelofibrosis, EM studies on bone marrow showed a strict topographic relatioship between the presence of clusters of abnormal megakaryocytes and the increased number of fibroblasts and extracellular fibers. Megakaryocytes and platelets lacked .alpha.-granules while the plasma thromboglobuline level was 3 times the normal level. This suggested that the .alpha.-granular proteins were synthesized but not retained in .alpha.-granules. If this occurs, the increased marrow levels of platelet-derived growth factor and factor 4 would favor the proliferation of fibroblasts and the synthesis of collagen, and thereby promote myelofibrosis. After therapy-induced remission, the number of marrow megakaryocytes decreased, the .alpha.-granules were normally produced, the plasma .beta.-thromboglobulin level was normal and the myelofibrosis disappeared. Apparently, during acute megakaryoblastic leukemia, an acquired gray-platelet syndrome occurs and the local excretion of .alpha.-granule proteins triggers the myelofibrosis.