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 relationship 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 thromboglobulin level was three 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. These observations suggest that during acute megakaryoblastic leukemia, an acquired gray-platelet syndrome occurs and that the local excretion of alpha-granule proteins triggers the myelofibrosis.