Growth characteristics of circulating hematopoietic progenitor cells from patients with essential thrombocythemia

Mazur, Eric Michael; Cohen, Jonah; Bogart, Lee

doi:10.1182/blood.v71.6.1544.1544

Cited by 34 publications

(9 citation statements)

References 21 publications

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“…In ET, the stem cell defect results in disproportionate and excessive megakaryocyte proliferation and platelet production, which appears to be independent of thrombopoietin. 1,16 The diagnosis of ET is established when the platelet count persistently exceeds 600 × 10 9 /L, no other demonstrable illness is likely to be the cause of reactive thrombocytosis, and thrombocytosis due to another myeloproliferative disorder (polycythemia vera, chronic myelocytic leukemia, or myelofibrosis) can be ruled out. 2,3,17 For personal use.…”

Section: Discussionmentioning

confidence: 99%

Medical Management of a Large Aortic Thrombus in a Young Woman With Essential Thrombocythemia

Fang

Agha

Lockridge

et al. 2001

Mayo Clinic Proceedings

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Aortic thrombus formation is rare in the patients with essential thrombocytosis (ET); therefore, no guidelines for its management have been established. Embolism from ET-associated large vessel thrombi is potentially lethal and has been managed surgically in a few reported cases. We describe herein a 45-year-old black woman with ET found to have a 3.5-cm, pedunculated intra-aortic thrombus at the thoracoabdominal junction. How to treat this potentially devastating aortic thrombus was a management dilemma. We believed, based on the patient's diagnosis of ET and the histology of similar thrombi in 1 reported series, that the aortic thrombus was a "white thrombus" consisting primarily of aggregated platelets with a minimal fibrin network and almost no entrapped erythrocytes. The patient was treated with aspirin, 325 mg daily, as a platelet antiaggregating agent and hydroxyurea, 1,500 mg daily, to reduce the platelet count to less than 450 x 10(9)/L. The thrombus resolved without severe thromboembolic events. To our knowledge, this is the first reported case of a large intra-aortic thrombosis associated with ET that has been successfully managed with medical therapy alone.

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Section: Discussionmentioning

confidence: 99%

Medical Management of a Large Aortic Thrombus in a Young Woman With Essential Thrombocythemia

Fang

Agha

Lockridge

et al. 2001

Mayo Clinic Proceedings

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“…All of the above indicates that the rnegakaryocyte progenitor growth is heterogenous in MPD. In our study the number of CFU-MK increased significantly with the addition of AAS to the plasma clot and agar cultures, which is consistent with previous data for ET (Komatsu et al, 1986: Juvonen et al, 1987Mazur et al, 1988;Gewirtz et al, 1983). This implies that optimal megakaryocyte colony development in MPD still requires exogenous growth factors.…”

Section: Discussionmentioning

confidence: 99%

“…blood and bone marrow of MPD could form spontaneous colonies in the absence of exogenous stimuli in vitro (Komatsu et al, 1986;Juvonen et al, 1987Juvonen et al, , 1993Grossi et al, 1987;Kimura et al, 1987;Han et al, 1987Han et al, , 1988Han et al, , 1989Battegay et al, 1989;Mazur et nf, 1988). Most observations (Komatsu et al, 1986;Juvonen et al, 1987Juvonen et al, , 1993Kimura et al, 1987;Battegay et al, 1989: Mazur et al, 1988, however, were made in cultures containing plasma or serum. Plasma and serum possess various factors acting on the growth of human megakaryocyte progenitors (Komatsu et al, 1986;Vainchenker et al, 1982;Messner et al, 1982;Solberg et al 1985;Yamasaki et al, 1987).…”

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confidence: 99%

Spontaneous megakaryocyte colony formation in myeloproliferative disorders is not neutralizable by antibodies against IL3, IL6 and GM‐CSF

et al. 1994

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Megakaryocyte progenitor growth in 42 patients with myeloproliferative disorders (MPD), including 23 essential thrombocythaemia (ET), eight polycythaemia vera (PV), six chronic myelogenous leukaemia (CML) and five primary myelofibrosis (PMF), was studied in vitro using plasma clot assay and serum-free agar culture. Spontaneous megakaryocyte colonies (CFU-MK) were found in 34/40 (80%) blood and 14/18 (77.8%) bone marrow plasma clot cultures, and also observed in 27/35 (77.1%) blood and 10/18 (55.6%) bone marrow serum-free agar cultures. In the blood of 27 patients with MPD (15 ET, four PV, four CML and four PMF) and the bone marrow of 10 patients (five ET, four CML and one PV), spontaneous colony formation was observed in both plasma clot and serum-free agar cultures. However, spontaneous CFU-MK was only found in plasma clot culture, but not in agar culture in two blood (one ET and one CML) and four bone marrow cultures (one ET, two PV, one CML). The colony numbers were greatly increased in the presence of aplastic anaemia serum (AAS) under both conditions. In 17 patients (12 ET, two CML and three PV) with spontaneous megakaryocyte colonies, anti-cytokine antibody neutralizing experiments were carried out in blood cultures. Anti-IL3, anti-IL6 and anti-GM-CSF antibody, alone or in combination, at different concentrations (1, 5 and 10 micrograms/ml), were added into plasma clot or agar cultures without exogenous stimulating growth factors. The results showed that the numbers of spontaneous megakaryocyte colonies were not significantly decreased in the presence of these monoclonal antibodies in the cultures. The data indicated that the megakaryocyte progenitor growth in MPD under in vitro conditions was heterogenous, and independent of exogenous stimulatory factors in most patients and that optimal megakaryocyte colony development in MPD still requires exogenous growth factors. Three possibilities are discussed with regard to the phenomenon that the spontaneous colony formation was not decreased with the addition of anti-IL3, anti-IL6 and anti-GM-CSF antibodies.

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“…[4-81. In this respect, it is not surprising that different investigators have arrived at different, and at times conflicting, conclusions [9][10][11][12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Essential thrombocythemia: Impaired regulation of megakaryocyte progenitors

Zauli

Catani

Gugliotta

et al. 1991

The International Journal of Cell Cloning

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In this paper, the in vitro growth of bone marrow early (megakaryocyte burst-forming units, BFU-meg) and late (megakaryocyte colony-forming units, CFU-meg) progenitors was evaluated in 18 essential thrombocythemia (ET) patients and 22 normal control subjects. BFU-meg clonality was demonstrated both in normal and ET bone marrows, cultivating these primitive progenitors at limiting dilutions in plasma clot assay: 1 to 7 BFU-meg/2.5 x 10(4) mononuclear non-adherent cells were observed, with a strong correlation in ET [r = 0.955 stimulated by recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) plus recombinant human interleukin (rhIL) 3], as well as in normal controls (r = 0.969). In order to clearly elucidate the in vitro response of ET megakaryocyte (meg) progenitors to recombinant growth factors, the interference of accessory cells (i.e., monocytes, T lymphocytes, and natural killer cells) and human serum were avoided by performing experiments on CD34+ cells in a serum-free fibrin clot assay. The number of both early and late meg progenitors in ET was significantly increased in response to rhIL-3, rhIL-3 plus rhIL-6, and rhIL-3 plus rhGM-CSF, but not in response to rhGM-CSF alone. Furthermore, both meg progenitors were investigated for their response to rh transfer growth factor (TGF)-beta 1, tested at concentrations from 0.01 to 10 ng/ml. rhTGF-beta 1 was able to inhibit CFU-meg and BFU-meg in a dose-response manner normal, whereas ET CFU-meg appeared less sensitive to the lower doses investigated (p less than 0.05) and ET BFU-meg were slightly reduced in number only at the higher concentrations of rhTGF-beta 1 (p less than 0.01). Our data suggest that the increased thrombopoiesis in ET may depend on an increased sensitivity of meg progenitors to some of the physiological growth factors and to a disrupted sensitivity to at least one negative regulator of megakaryocytopoiesis. Since these abnormalities involve both meg progenitors, this can be considered a demonstration that the neoplastic event hits the most primitive hemopoietic progenitors.

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Growth characteristics of circulating hematopoietic progenitor cells from patients with essential thrombocythemia

Cited by 34 publications

References 21 publications

Medical Management of a Large Aortic Thrombus in a Young Woman With Essential Thrombocythemia

Medical Management of a Large Aortic Thrombus in a Young Woman With Essential Thrombocythemia

Spontaneous megakaryocyte colony formation in myeloproliferative disorders is not neutralizable by antibodies against IL3, IL6 and GM‐CSF

Essential thrombocythemia: Impaired regulation of megakaryocyte progenitors

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