Normal thrombopoietin and its receptor (c-mpl) genes in children with essential thrombocythemia

Randi, Maria Luigia; Putti, Mc; Pacquola, Enrica; Luzzatto, Guido; Zanesco, Luigi; Fabris, Fabrizio

doi:10.1002/pbc.20185

Cited by 13 publications

(5 citation statements)

References 22 publications

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“…Previous investigations on TPO concentrations in chronic myeloproliferative disorders have shown that serum/plasma levels are slightly above or within the range of normal individuals 11-25. Our results agree well with these previously published concentrations when the same assay, as we used here, has been employed.…”

Section: Discussionsupporting

confidence: 93%

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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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Section: Discussionsupporting

confidence: 93%

“…Serum or plasma levels of TPO are often, but not always, raised in MPD 11-20; 21-25, with the highest levels being observed in MF 24, 26. Likewise, TPO concentrations are often high in reactive thrombocytosis 13, 14, 18, 22.…”

Section: Introductionmentioning

confidence: 99%

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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“…The JAK2 V617F mutation was genotyped using allele‐specific polymerase chain reaction (PCR) in DNA extracted from isolated granulocytes (Randi et al , ) and the mutant allele burden was measured by quantitative real time‐PCR (Teofili et al , ). The MPL (Randi et al , ; Beer et al , ) and CALR (Klampfl et al , ) mutations were sought by direct sequencing. The X‐chromosome inactivation pattern (X‐CIP) in granulocytes was studied in females using the human androgen receptor gene ( AR , also termed HUMARA) polymorphism method, as described elsewhere (Randi et al , ).…”

Section: Methodsmentioning

confidence: 99%

Are all cases of paediatric essential thrombocythaemia really myeloproliferative neoplasms? Analysis of a large cohort

et al. 2015

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SummarySporadic essential thrombocythaemia (ET) is rare in paediatrics, and the diagnostic and clinical approach to paediatric cases cannot be simply copied from experience with adults. Here, we assessed 89 children with a clinical diagnosis of ET and found that 23 patients (25Á8%) had a clonal disease. The JAK2 V617F mutation was identified in 14 children, 1 child had the MPL W515L mutation, and 6 had CALR mutations. The monoclonal X-chromosome inactivation pattern was seen in six patients (two with JAK2 V617F and two with CALR mutations). The other 66 patients (74Á2%) had persistent thrombocytosis with no clonality. There were no clinical or haematological differences between the clonal and non-clonal patients. The relative proportion of ET-specific mutations in the clonal children was much the same as in adults. The higher prevalence of nonclonal cases suggests that some patients may not have myeloproliferative neoplasms, with significant implications for their treatment.

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“…A significant proportion of cases occur in families with other cases of MPD (familial MPD) [39]. Cytogenetic alterations or the spontaneous growth of endogenous erythroid colonies (EEC) have never been described in children, and no TPO and c-MPL gene mutations were found in seven sporadic cases [40]. In a cohort of 20 cases, our group found four children with the JAK2V617F mutation, which indicates a lower rate than in adults [19].…”

Section: Life Expectancy Prognostic Factors and Progression To Leukmentioning

confidence: 96%

Essential thrombocythemia: past and present

Fabris

Randi

2009

Intern Emerg Med

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Essential thrombocythemia (ET) is a clonal myeloproliferative disorder characterized by sustained increase in platelet number and tendency for thromboembolism. A somatic point mutation that causes a constitutive activation of the JAK2 gene is found in one in two ET patients. ET is more common in women, its incidence being 0.6-2.5/100,000 patient/year and the median age at diagnosis is 65-70 years. ET can affect all age groups, including children (0.09 cases/year), and is often diagnosed in the third-fourth decade of life. Rare cases of familial ET have been reported. Miscarriages are 3-4 times more common among women with ET than in the general population, especially in patients carrying JAK2V617F. Microvascular disturbances are typical of ET, but a major thrombosis (2/3 arterial and 1/3 venous; 1, 2-3% patient/year) is the main cause of morbidity and mortality. Age over 60 years and/or previous thrombosis are validated risk factor for thrombosis. Hemorrhages occur in 0.33% patient/year, mainly in those with a platelet count over 1,500 x 10(9)/L. Progression to myelofibrosis and leukemia is more common in patients carrying the JAK2V617F mutation, and is estimated to occur in 0.16% and 0.12% patient/year, respectively. The ET-related mortality ratio with respect to the general population is 1:1, while for polycythemia vera it is 1.6:1. Low-dose aspirin is useful for microvascular disturbances, and in the primary and secondary prevention of major thrombosis in high-risk patients, but it is not recommended in patients with a platelet count over 1,500 x 10(9)/L. Hydroxyurea is used as first-line treatment in high-risk patients. Other drugs available are alpha-interferon, anagrelide, pipobroman and busulphan.

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Normal thrombopoietin and its receptor (c-mpl) genes in children with essential thrombocythemia

Abstract: High platelet count in our series of sporadic ET of childhood is not due to an abnormality either of TPO or c-mpl gene.

Cited by 13 publications

References 22 publications

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

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

Are all cases of paediatric essential thrombocythaemia really myeloproliferative neoplasms? Analysis of a large cohort

Essential thrombocythemia: past and present

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