title: Plasma thrombopoietin (TPO) levels and expression of TPO receptor on platelets in patients with myelodysplastic syndromes.
abstract: 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 125I-TPO. The MDS patients had higher plasma TPO levels (7.0 +/- 9.3 fmol/ml) than 52 normal subjects (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 platelet counts in these groups. The plasma TPO level correlated inversely with 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 significantly 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. 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.
authors.affiliation: Third Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Tamura
authors.forename: K
authors.initials: K
authors.lastname: Ogata
authors.forename: S
authors.initials: S
authors.lastname: Luo
authors.forename: K
authors.initials: K
authors.lastname: Nakamura
authors.forename: N
authors.initials: N
authors.lastname: Yokose
authors.forename: K
authors.initials: K
authors.lastname: Dan
authors.forename: K
authors.initials: K
authors.lastname: Tohyama
authors.forename: Y
authors.initials: Y
authors.lastname: Yoshida
authors.forename: H
authors.initials: H
authors.lastname: Hamaguchi
authors.forename: H
authors.initials: H
authors.lastname: Sakamaki
authors.forename: T
authors.initials: T
authors.lastname: Kuwaki
authors.forename: T
authors.initials: T
authors.lastname: Tahara
authors.forename: T
authors.initials: T
authors.lastname: Kato
authors.forename: T
authors.initials: T
authors.lastname: Nomura
mesh_terms: D001792:Blood Platelets / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000097:blood*; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; D013926:Thrombopoietin / Q000032:analysis*
chemical_list: D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; D013926:Thrombopoietin