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

Abstract

Summary. Data on endogenous thrombopoietin (TPO) levels and their regulation in myelodysplastic syndromes (MDS) are sparse. We examined the plasma TPO level of 85 MDS patients by a sensitive enzyme immunoassay and the platelet expression of TPO receptor (TPO-R) protein, which metabolizes endogenous TPO, in 19 MDS patients with an equilibrium binding assay using 125 I-TPO. The MDS patients had higher plasma TPO levels (7·0 Ϯ 9·3 fmol/ml) than 52 normal subjects (P < 0·0001). Refractory anaemia (RA) patients (n ¼ 39) had higher plasma TPO levels than patients (n ¼ 28) with RA with excess blasts (RAEB) or RAEB in transformation (RAEB-t) (P ¼ 0·0002), irrespective of similar platelet counts in these groups. The plasma TPO level correlated inversely with the platelet count in RA patients (P ¼ 0·0027) but not in RAEB and RAEB-t patients (P ¼ 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 significantly smaller in 19 MDS patients (17·5 Ϯ 13·3) than in normals (P ¼ 0·0014), but similar between RA patients and patients with RAEB and RAEB-t. Further, 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 contribute to elevated plasma TPO levels in MDS, and a regulatory pathway for circulating TPO other than platelet TPO-R and marrow megakaryocytes, such as blasts expressing TPO-R, may operate in RAEB/RAEB-t.

Increased plasma thrombopoietin levels in patients with myelodysplastic syndrome: a reliable marker for a benign subset of bone marrow failure

“…28 Increased production and destruction of platelets may accelerate TPO consumption in patients with RAEB, leading to a decrease in plasma TPO levels. Although one report demonstrated increased TPO receptors on the megakaryocytes of MDS patients using flow cytometry, 14 we were unable to reproduce their results (data not shown).…”

“…13,14 While patients with RAEB had consistently low TPO levels, patients with low-risk MDS (RCUD, RCMD, and MDS-U) produced highly variable results. Feng et al recently demonstrated similar variability among patients with hypoplastic MDS and reported the usefulness of TPO in distinguishing hypoplastic MDS from AA; 21 however, the significance of high TPO levels in a subset of patients with low-risk MDS was not the focus of the authors' attention.…”

“…Previous studies showed that plasma levels of thrombopoietin (TPO), a critical regulator of thrombopoiesis, were elevated in patients with AA 11 but remained low in patients with MDS despite the presence of severe thrombocytopenia. [12][13][14] The low TPO levels in MDS patients have been connected to an increase in megakaryocytes or TPO receptors on megakaryocytes, 13 but no studies have focused on the possibility of different TPO levels among MDS subtypes. Patients with low-risk MDS could have high TPO levels and respond to IST as AA patients do.…”

Cytokine signature profiles in acquired aplastic anemia and myelodysplastic syndromes

“…3,4 To date, measurements of soluble circulating mediating factors in marrow failure have been limited largely to one or two cytokines in AA [5][6][7][8][9] and MDS. 10,11 Because of the complex array of proteins involved in an immune response, the measurement of a single cytokine is likely insufficient to assess alterations in disease. We conducted a comprehensive analysis of 31 cytokines, chemokines, and growth factors in the plasma of healthy volunteers, AA, and MDS patients.…”

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

“…In the past, studies on TPO levels in MDS showed significantly high levels in RA patients and generally low levels in RAEB and RAEB-t patients. 15,30,31 It was also reported that a significant inverse relationship between the TPO concentration and platelet count exists in RA patients, but not in RAEB or RAEB-t patients. However, in this study, both RAEB and CMML patients showed high TPO levels when their CFU-meg were reduced, suggesting no difference among subtypes.…”