Progressive preleukemia presenting amegakaryocytic thrombocytopenic purpura: association of the 5q- syndrome with a decreased megakaryocytic colony formation and a defective production of Meg-CSF.
The authors present a patient with the typical clinical picture of an acquired amegakaryocytic thrombocytopenic purpura. After 16 months of observation, the patient developed acute myelomonocytic leukemia. During the preleukemic phase and after progression to overt leukemia, serial in-vitro analyses of megakaryocytic, granulocytic, erythrocytic and T-lymphocytic colony growth were carried out in a microagar culture system. At presentation, a marked diminution of CFU-M was observed, whereas CFU-E, BFU-E, CFU-C and CFU-TL were in the normal range. The CFU-M number remained at its low level during the whole observation period. The CFU-C number declined steadily during the preleukemic period, while BFU-E, CFU-E and CFU-TL remained constant until January 1985 when the patient developed AML. After progression to overt leukemia, a distinct reduction became evident in all colony-forming cells. Cytogenetic studies performed during the preleukemic phase indicated the presence of a 5q- chromosome. The authors submit evidence here that the patient was not only characterized by defective megakaryocytic colony formation but also by a deficiency of functional megakaryocyte colony-stimulating activity. No humoral or cellular inhibitors of CFU-M colony formation were found. It is concluded that in preleukemia with a 5q- chromosome the megakaryocytic cell lineage may be involved in the process that precedes overt leukemia at an earlier time than cells of granulocytic and erythrocytic lineages. In addition, it is shown here that megakaryocytopoiesis during the preleukemic period can be characterized by two different defects: first, an intrinsic megakaryocytic stem cell defect and, second, a deficiency of functional megakaryocytic colony-stimulating activity.
D000328:Adult; D000954:Antigens, Surface / Q000032:analysis; D001853:Bone Marrow / Q000276:immunology; D002872:Chromosome Deletion; D002895:Chromosomes, Human, Pair 5; D003115:Colony-Stimulating Factors / Q000378:metabolism; D003937:Diagnosis, Differential; D005260:Female; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008533:Megakaryocytes / Q000378:metabolism / Q000473:pathology*; D011289:Preleukemia / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D011697:Purpura, Thrombotic Thrombocytopenic / Q000175:diagnosis*; D013577:Syndrome; D013601:T-Lymphocytes / Q000473:pathology
D000954:Antigens, Surface; D003115:Colony-Stimulating Factors