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

Abstract

We studied both serum-free colony-forming unit-megakaryocyte (CFU-meg) numbers and serum thrombopoietin (TPO) levels in 14 patients with aplastic anemia (AA), 37 patients with myelodysplastic syndromes (MDS) and 23 patients with idiopathic thrombocytopenic purpura (ITP) to assess thrombopoiesis in these thrombocytopenic disorders. The mean CFU-meg numbers were lower in AA and MDS patients (10.7 ؎ 11.4 and 42.3 ؎ 58.5/10 5 BMLD cells) than in healthy controls (103.1 ؎ 57.3/10 5 BMLD cells) (P Ͻ 0.0001 and P = 0.0053, respectively), although they were distributed variably in MDS. ITP patients showed higher CFU-meg numbers (223.2 ؎ 143.5/10 5 BMLD cells) (P = 0.017). The mean TPO concentrations were higher in both AA (986.8 ؎ 500.8 pg/ml) and MDS patients (838.2 ؎ 639.1 pg/ml) than in healthy controls (80.7 ؎ 38.8 pg/ml) (P Ͻ 0.0001), although they were distributed from high to low in MDS. ITP patients showed a slight elevation of TPO (123.1 ؎ 55.3 pg/ml) P = 0.0106). The TPO levels was inversely correlated to both platelet counts and CFU-meg numbers (correlative coefficient (CC): −0.719 and −0.682, P Ͻ 0.0001) in AA, but not in ITP. In MDS, the inverse correlation to TPO was stronger in CFU-meg (CC: −0.678, P Ͻ 0.0001) than in platelet counts (CC: −0.538, P = 0.0014), suggesting that CFU-meg plays an important role in regulating TPO production in this heterogenous disorder. CFUmeg and TPO may provide useful information for understanding thrombopoiesis of MDS, especially for application of TPO.

Ultrastructural study shows morphologic features of apoptosis and para-apoptosis in megakaryocytes from patients with idiopathic thrombocytopenic purpura

“…Previous studies on the number of CFUMks in chronic ITP showed conflicting results, depending on the assay that was used, the stage (acute or chronic) of the disease, and the refractoriness of the ITP to therapy. Several authors 27,28 found a significant increase in number of CFU-Mks in chronic ITP patients. Others 29,30 reported a reduced number of CFU-Mks in chronic ITP.…”

Prospective screening of 205 patients with ITP, including diagnosis, serological markers, and the relationship between platelet counts, endogenous thrombopoietin, and circulating antithrombopoietin antibodies

“…Serum concentrations of endogenous TPO (eTPO) reflect its constitutive production by the liver and its clearance through binding and internalization by Mpl, the TPO receptor found on the surfaces of platelets and megakaryocytes [10,11]. Several studies have reported increased amounts of eTPO in patients with thrombocytopenia secondary to aplastic anemia, amegakaryocytic thrombocytopenia, and myeloablative chemotherapy [12][13][14][15][16][17][18][19]. In contrast, eTPO levels are not increased in patients with ITP, despite the markedly reduced number of circulating platelets [14][15][16]20].…”

Evidence for reduced B-cell progenitors in early (low-risk) myelodysplastic syndrome

“…25,26 In keeping with a stem/myeloid progenitor defect, there is reduced in vitro long-term culture-initiating cell activity 27 and decreased numbers of erythroid, granulocyte, and megakaryocyte colonies. 28,29 Given the heterogeneity of low-risk MDS, it is likely that the mode of pathogenesis will differ between individual patients. However, the functional consequence of bone marrow proliferation and dysplasia could alight on a final common pathway, which may allow detection of common changes among apparently disparate patients.…”