Abnormal megakaryopoiesis in patients with myelodysplastic syndromes: analysis of cellular and humoral defects

Abstract

In 13 patients with myelodysplastic syndrome (MDS) mature and immature erythropoietic (CFU-E, BFU-E), granulopoietic (CFU-GM) and megakaryopoietic (CFU-Meg) colony formation from human bone marrow mononuclear cells was evaluated in a microagar culture system. All but three patients exhibited abnormal CFU-Meg. The defect of CFU-Meg paralleled the reduction of BFU-E, whereas CFU-GM number declined to a lesser extent. Not only the CFU-Meg number, but also the number of megakaryocytes (Mk) per colony was reduced suggesting an additional functional CFU-Meg defect. Megakaryocytic growth factor (Meg-CSF) abnormalities in MDS patients were detected using normal nonadherent T-lymphocyte depleted bone marrow cells as target cells for serum testing. Even for sera from patients with a reduction of platelets and bone marrow megakaryocytes Meg-CSF levels were not increased. No cellular or humoral inhibition could be detected in an MDS patient with a 5q- karyotype, who had an isolated defect of the megakaryocytic cell lineage at presentation. Some patients revealed a spontaneous formation of mixed erythrocytic, granulocytic and megakaryocytic clusters in the presence of fetal calf serum or autologous patient serum, probably representing autonomous proliferation of the malignant clone. In conclusion, both cellular and humoral factors can cause abnormalities of the megakaryocytic cell lineage in MDS patients.

Colony-forming unit-megakaryocyte (CFU-meg) numbers and serum thrombopoietin concentrations in thrombocytopenic disorders: an inverse correlation in myelodysplastic syndromes

“…18,28 In addition, the number of megakaryocytes per colony was also reported to be reduced. 29 Consistent with these studies, two-thirds of the patients, group III in our study, showed reduced numbers of CFU-meg; most of them were small colonies. However, there were some patients with normal or increased numbers of CFU-meg (group II and I) and thrombocytopenia simultaneously, suggesting poor platelet production in spite of sufficient megakaryocytic progenitors.…”

Three-Lineage Hemopoietic Precursor Cells and Effectiveness of Recombinant Human Erythropoietin in Patients with Myelodysplastic Syndromes.

“…In RAEB-T, two patients (cases 8,9) showed no increase in colony growth at each higher concentration, while one patient (case 7) showed a significant increase at 100 ng/ml of G-CSF.…”

Endogenous serum thrombopoietin concentrations in patients with myelodysplastic syndromes

“…include ineffective hemopoiesis, 23 impaired responsiveness to Elevated TPO concentrations were found in eight out of 12 patients growth factor stimulation, 24 and inhibitory mechanisms with decreased megakaryopoiesis and in only one out of the eight mediated by microenvironmental conditions including tumor patients with normal or increased megakaryopoiesis.…”