Strong inverse correlation between serum TPO level and platelet count in essential thrombocythemia

Tomita, Naoto; Motomura, Shigeki; Sakai, Rika; Fujimaki, Katsumichi; Tanabe, Juichi; Fukawa, H; Harano, Hiroshi; Kanamori, Heiwa; Ogawa, Kouji; Mohri, Hiroshi; Maruta, Atsuo; Kodama, Fumio; Ishigatsubo, Yoshiaki; Tahara, Tomoyuki; Kato, Takashi

doi:10.1002/(sici)1096-8652(200003)63:3<131::aid-ajh4>3.0.co;2-#

Cited by 15 publications

(5 citation statements)

References 23 publications

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“…The decrease in surface expression of c-Mpl in ET may be responsible for elevated TPO levels through lack of ligand binding; in fact, an inverse correlation between TPO and c-Mpl has been reported in ET. 37 However, TPO levels increased in secondary thrombocytosis, perhaps as an acute-phase reactant. 38,39 We observed normal c-Mpl expression in patients with RT; hence, the increased TPO levels observed in these patients might be the cause of their thrombocytosis.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic and prognostic value of bone marrow angiogenesis and megakaryocyte c-Mpl expression in essential thrombocythemia

Mesa

Hanson

et al. 2002

Blood

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The lack of diagnostic certainty in some patients makes it difficult to distinguish between primary and secondary forms of thrombocytosis. To augment current diagnostic studies for thrombocytosis, we retrospectively evaluated clinical records and bone marrow trephine specimens of 183 patients with thrombocytosis-164 with essential thrombocythemia (ET), 19 with reactive thrombocytosis (RT)-for bone marrow angiogenesis, bone marrow megakaryocyte c-Mpl staining, and morphologic evidence of megakaryocyte proliferation. Angiogenesis was increased in patients with ET compared with healthy controls (P < .0001) and patients with RT (P ‫؍‬ .006). In addition, an increase in angiogenesis was associated with certain disease features such as splenomegaly (P ‫؍‬ .004) and reticulin fibrosis (P ‫؍‬ .005). Decreased megakaryocyte c-Mpl staining was observed in a heterogeneous pattern in ET compared with healthy controls (P < .0001) and RT (P < .0001). Histologic stratifying criteria incorporating increased angiogenesis, decreased megakaryocyte c-Mpl expression, and marked megakaryocyte proliferation in the bone marrow was highly sensitive (97%) and specific (95%) for distinguishing ET from RT (P < .0001

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Section: Discussionmentioning

confidence: 99%

Diagnostic and prognostic value of bone marrow angiogenesis and megakaryocyte c-Mpl expression in essential thrombocythemia

Mesa

Hanson

et al. 2002

Blood

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“…Our results indicated an association between the TPOR, but not the TPO, allele distribution to PLT count. Accumulating evidence indicates that the TPO-TPOR system not only regulates the number of circulating platelets but also affects the production of red and white blood cells in animal models and some human hematological diseases [18][19][20][21][22][23][24]. Not only is the TPO level inversely related to PLT count [15][16][17], but PLT count itself has a feedback effect on the level of TPO [30].…”

Section: Discussionmentioning

confidence: 99%

“…Thrombopoietin (TPO) has been shown to be a major physiological regulator of circulating PLT count. TPO primarily affects the proliferation and differentiation of megakaryocytes, and plasma TPO levels are inversely related to PLT count in normal human studies and animal models [15][16][17][18]. TPO functions by binding to its receptor (TPOR or Mpl), which is a member of the hematopoietin receptor superfamily [19].…”

Section: Introductionmentioning

confidence: 99%

Association of single nucleotide polymorphisms in the thrombopoietin‐receptor gene, but not the thrombopoietin gene, with differences in platelet count

et al. 2004

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Little is known about the mechanisms explaining the wide variation in platelet counts (PLT) and other hematologic parameters in humans. We previously showed that the sexbased difference in hematocrit was associated with nucleotide variation in the erythropoietin receptor gene (EPOR). We sought to identify new polymorphisms of the human thrombopoietin (TPO) and thrombopoietin receptor (TPOR) genes to determine any associations with blood PLT counts. We screened TPO and TPOR for polymorphisms using single-strand conformation polymorphism (SSCP) and DNA sequencing. Association of polymorphisms was studied in 304 normal subjects with low or high PLT counts. Distribution of allelic frequency was analyzed by the Chi-square statistic. Single nucleotide polymorphisms (SNPs) with two alleles were found in TPO and TPOR. The TPO SNP was a G to A transition at nucleotide 5753, and the TPOR SNP was a C to A transversion at position 550 in the 5 0 -promoter area. The allelic frequencies were 0.54 for G and 0.46 for A of TPO, and 0.62 for C and 0.38 for A of TPOR in a Caucasian population. The frequency of the TPOR allele ''C'' was significantly higher in subjects with high PLT count (>258 k/mm ). In contrast, the frequency of the TPO alleles was not related to blood PLT counts. An association of TPO and TPOR allele distribution to red and white blood cell parameters was seen. These new SNPs found for the human TPO and TPOR genes help explain variations in blood PLT counts and may be useful in patient studies related to the roles of TPO and/or TPOR in disease. Am.

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“…A few reports have described higher TPO levels in treated compared to untreated MPD patients 15, 17, 12. In some of these studies, an inverse relation between blood platelet counts and TPO was observed 16, 26 but just as often there was no correlation 13, 19. A role for TPO for emergence of MF has also been suggested, based on results from studies with mice with engineered TPO overproduction 27-29.…”

Section: Introductionmentioning

confidence: 98%

TPO, but not soluble-IL-6 receptor, levels increase after anagrelide treatment of thrombocythemia in chronic myeloproliferative disorders

Palmblad¹,

Björkholm²,

Kutti³

et al. 2008

Int. J. Med. Sci.

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Anagrelide is often used in the treatment of thrombocythemia in myeloproliferative disease (MPD), but information concerning effects of treatment on cytokines involved in regulation of blood platelet levels is limited. Here, we investigated serum levels of thrombopoietin (TPO) and soluble IL-6 receptor (sIL-6R) in relation to response to treatment with and plasma concentrations of anagrelide. Samples from 45 patients with thrombocythemia due to MPD (ET=31, PV=14), being treated with anagrelide for 6 months, were analyzed for TPO, sIL-6R and anagrelide levels. The mean baseline platelet count was 983x10 9 /L. A reduction of platelets to <600 in asymptomatic or <400 x 10 9 /L in symptomatic patients was defined as a complete remission (CR), a reduction with >50% of baseline as partial remission, and <50% reduction as failure. At 6 months, 35 patients were in CR, 1 had a partial remission and 9 were treatment failures. For all patients, there was an increase in TPO of 44% from baseline; this change was more pronounced for patients with partial remission and failure. sIL-6R levels did not change significantly. There was no correlation between levels of anagrelide and cytokine levels at 6 months, and changes of cytokine levels did not relate to changes of platelet counts. Thus, a pronounced increase of TPO levels after 6 months of anagrelide treatment indicated that this treatment affected a major regulatory mechanism for megakaryocyte and platelet formation in MPD.

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Strong inverse correlation between serum TPO level and platelet count in essential thrombocythemia

Cited by 15 publications

References 23 publications

Diagnostic and prognostic value of bone marrow angiogenesis and megakaryocyte c-Mpl expression in essential thrombocythemia

Diagnostic and prognostic value of bone marrow angiogenesis and megakaryocyte c-Mpl expression in essential thrombocythemia

Association of single nucleotide polymorphisms in the thrombopoietin‐receptor gene, but not the thrombopoietin gene, with differences in platelet count

TPO, but not soluble-IL-6 receptor, levels increase after anagrelide treatment of thrombocythemia in chronic myeloproliferative disorders

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