Thrombopoietin and myelodysplastic syndromes.

Thrombopoietin (TPO), a major cytokine involved in megakaryocystopoiesis/thrombopoiesis, may be effective for the treatment of thrombocytopenia associated with myelodysplastic syndromes (MDS). We reviewed the available data relating to the therapeutic potential of TPO for MDS and found the following. The endogenous TPO level is elevated in MDS patients, especially in those with refractory anemia (RA). In RA patients, but not in patients with RA with excess blasts (RAEB) or RAEB in transformation (RAEB-t), both the platelet and megakaryocyte counts correlate inversely with the endogenous TPO level. This scenario indicates that the physiological mechanism for regulating the endogenous TPO level is conserved, at least in part, in RA patients. The number of TPO receptors (TPO-R) expressed on platelets and CD41+ and/or CD34+ cells in MDS is reduced to nearly half the number present in normal subjects. This is consistent with the finding that TPO-induced in vitro megakaryocytopoiesis is not uniformly observed in MDS. Meanwhile, in some patients with RAEB, RAEB-t, or chronic myelomonocytic leukemia, blasts have the TPO-R mRNA and probably TPO-R protein. This fact may explain the lack of correlation between the endogenous TPO level and the platelet and megakaryocyte counts in RAEB and RAEB-t and suggests that TPO may induce blast proliferation in some cases. These findings may be of use when designing a clinical trial of TPO for MDS.