Endogenous serum thrombopoietin concentrations in patients with myelodysplastic syndromes

Zwierzina, Heinz; Rollinger-Holzinger, Ingrid; Nuessler, V.; Herold, Manfred; Meng, Yinping

doi:10.1038/sj.leu.2400901

Cited by 21 publications

(14 citation statements)

References 2 publications

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“…The MDS subtypes of the subjects examined in those reports were not described. Recently, Zwierzina et al (1998 ) reported the blood TPO levels in 69 MDS patients. Because their TPO assay was much less sensitive than ours, TPO was able to be detected in the blood of only 14/69 cases.…”

Section: Discussionmentioning

confidence: 99%

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

Tamura¹,

Ogata²,

Luo³

et al. 1998

Br J Haematol

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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.

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Section: Discussionmentioning

confidence: 99%

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

Tamura¹,

Ogata²,

Luo³

et al. 1998

Br J Haematol

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“…In many MDS cases, megakaryocyte progenitor growth was unresponsive to recombinant TPO. 22,24 This defective response is probably due to deregulated TPOreceptor-mediated signaling pathways, 25 as a lack of serum TPO, 26 a decreased expression of c-mpl (TPO-receptor) 22 or mutations in c-mpl 25 have been excluded.…”

Section: Apoptosis In Mds: Evidence and Controversiesmentioning

confidence: 99%

Megakaryocytic dysfunction in myelodysplastic syndromes and idiopathic thrombocytopenic purpura is in part due to different forms of cell death

et al. 2006

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Platelet production requires compartmentalized caspase activation within megakaryocytes. This eventually results in platelet release in conjunction with apoptosis of the remaining megakaryocyte. Recent studies have indicated that in low-risk myelodysplastic syndromes (MDS) and idiopathic thrombocytopenic purpura (ITP), premature cell death of megakaryocytes may contribute to thrombocytopenia. Different cell death patterns have been identified in megakaryocytes in these disorders. Growing evidence suggests that, besides apoptosis, necrosis and autophagic cell death, may also be programmed. Therefore, programmed cell death (PCD) can be classified in apoptosis, a caspase-dependent process, apoptosis-like, autophagic and necrosis-like PCD, which are predominantly caspase-independent processes. In MDS, megakaryocytes show features of necrosis-like PCD, whereas ITP megakaryocytes demonstrate predominantly characteristics of apoptosis-like PCD (para-apoptosis). Triggers for these death pathways are largely unknown. In MDS, the interaction of Fas/Fas-ligand might be of importance, whereas in ITP antiplatelet autoantibodies recognizing common antigens on megakaryocytes and platelets might be involved. These findings illustrate that cellular death pathways in megakaryocytes are recruited in both physiological and pathological settings, and that different forms of cell death can occur in the same cell depending on the stimulus and the cellular context. Elucidation of the underlying mechanisms might lead to novel therapeutic interventions.

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“…6,[13][14][15][16][17][18][19][20][21][22][23][24][25] The overexpression of c-mpl was shown to be a poor prognostic factor for patients with AML. 24 In patients with myelofibrosis, c-mpl levels correlated with the degree of fibrosis.…”

mentioning

confidence: 99%

Expression of thrombopoietin and its receptor (c-mpl) in chronic myelogenous leukemia

Kaban

Kantarjian

Talpaz

et al. 2000

Cancer

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Endogenous serum thrombopoietin concentrations in patients with myelodysplastic syndromes

Cited by 21 publications

References 2 publications

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

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

Megakaryocytic dysfunction in myelodysplastic syndromes and idiopathic thrombocytopenic purpura is in part due to different forms of cell death

Expression of thrombopoietin and its receptor (c-mpl) in chronic myelogenous leukemia

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