Plasma thrombopoietin (TPO) levels and expression of TPO receptor on platelets in patients with myelodysplastic syndromes

Data on endogenous thrombopoietin (TPO) levels and their regulation in myel odysplastic syndromes (MDS) are sparse. We examined the plasma TPO level of 85 MDS patients by a sensitive enzyme immunoassay and the platelet express ion of TPO receptor (TPO-R) protein, which metabolizes endogenous TPO, in 1 9 MDS patients with an equilibrium binding assay using I-125-TPO. The MDS p atients had higher plasma TPO levels (7.0 +/- 9.3 fmol/ml) than 52 normal s ubjects (P < 0.0001). Refractory anaemia (RA) patients (n = 39) had higher plasma TPO levels than patients (n = 28) with RA with excess blasts (RAEB) or RAEB in transformation (RAEB-t) (P = 0.0002), irrespective of similar pl atelet counts in these groups, The plasma TPO level correlated inversely wi th the platelet count in RA patients (P = 0.0027) but not in RAEB and RAEB- t patients (P = 0.7865). These data suggest that the physiological pathway for TPO production and metabolism is conserved, at least partially, in RA, but deranged in RAEB/RAEB-t. The number of TPO-R per platelet was significa ntly smaller in 19 MDS patients (17.5 +/- 13.3) than in normals (P = 0.0014 ), but similar between RA patients and patients with RAEB and RAEB-t. Furth er, the bone marrow megakaryocyte count, determined in 31 MDS patients, was quite similar between RA patients and patients with RAEB or RAEB-t. Thus, in addition to thrombocytopenia, a reduced platelet TPO-R number may contri bute to elevated plasma TPO levels in MDS, and a regulatory pathway for cir culating TPO other than platelet TPO-R and marrow megakaryocytes, such as b lasts expressing TPO-R, may operate in RAEB/RAEB-t.