Identification and cloning of a megakaryocyte growth and development factor that is a ligand for the cytokine receptor MpI

Bartley, Timothy D.; Bogenberger, Jakob; Hunt, Pamela S.; Li, Y.-S.; Lu, Hsieng S.; Martin, Frank; Chang, Ming-Shi; Samal, Babru; Nichol, JL; Swift, Susan; Johnson, Malcolm; Hsu, Rou-Yin; Parker, Vann P.; Suggs, Sid; Skrine, Jim; Merewether, Lee Anne; Clogston, Chris; Hsu, Eric; Hokom, Martha; Hornkohl, A.; Choi, Esther; Pangelinan, Michael; Sun, Yu; Mar, V L; McNinch, Jennifer; Simonet, Lizette; Jacobsen, Frederick W.; Xie, Chunshan; Shutter, John R.; Chute, Hilary; Basu, Rita; Selander, Lars; Trollinger, David; Sieu, Leang C.; Padilla, Danielle J.; Trail, Geraldine; Elliott, Gary; Izumi, Ryutaro; Covey, Todd; Crouse, Jill; Garcia, Andy; Xu, Weixin; Castillo, J del; Biron, Julie; Cole, Sean; Hu, Mickey C.T.; Pacifici, Robert E.; Ponting, I. L. O.; Saris, Christiaan J. M.; Wen, Duanzhi; Yung, Yee Pang; Lin, Huawen; Rosselman, R.A.

doi:10.1016/0092-8674(94)90450-2

Cited by 946 publications

(486 citation statements)

References 36 publications

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“…[1][2][3][4][5][6] It stimulates proliferation of megakaryocytic progenitors, induces megakaryocytic differentiation, and increases platelet production in vivo and in vitro, [1][2][3][4][5]7 and is most likely the primary regulator of megakaryocytopoiesis and platelet production. However, the regulatory mechanism of platelet production by TPO is not clearly understood at present.…”

Section: Introductionmentioning

confidence: 99%

Serum thrombopoietin levels in patients correlate inversely with platelet counts during chemotherapy-induced thrombocytopenia

et al. 1998

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We studied serum thrombopoietin (TPO) levels and circulating numbers of platelet during five courses of myelosuppressive post-remission chemotherapy in three patients with acute leukemia in complete remission. Serum TPO levels were measured by a newly developed and sensitive sandwich enzyme-linked immunosorbent assay. In all courses, serum TPO levels changed reciprocally with the platelet counts. When platelets were transfused into patients near the time of platelet nadir, the TPO levels dropped temporarily, while platelet counts temporarily increased. In addition, platelets obtained after transfusion in a thrombocytopenic patient showed lower binding to biotinylated TPO than donor platelets prior to the transfusion. The finding indicated that the TPO receptors were saturated with endogenous TPO of the patient with a high serum TPO level. These results suggest that the platelet mass directly regulates serum TPO levels by receptor-mediated absorption and is one of the major regulators of serum TPO levels in humans.

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Section: Introductionmentioning

confidence: 99%

Serum thrombopoietin levels in patients correlate inversely with platelet counts during chemotherapy-induced thrombocytopenia

et al. 1998

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“…[1][2][3][4] This hematopoietic growth factor appears as the homeostatic regulator of platelet production. Indeed, homozygous TPO or c-mpl knock-out mice exhibit a profound but not lethal thrombocytopenia.…”

Section: Introductionmentioning

confidence: 99%

Major effects of TPO delivered by a single injection of a recombinant adenovirus on prevention of septicemia and anemia associated with myelosuppression in mice: risk of sustained expression inducing myelofibrosis due to immunosuppression

et al. 1998

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Adenoviral vectors may be useful tools to deliver a cytokine an improvement in the leukopenia since all control mice in vivo. A single intravenous injection of an adenovirus vecdied from septicemia. However, the effects of TPO may tor containing the human thrombopoietin (TPO) cDNA be potentiated by the release of inflammatory cytokines (AdRSVhuTPO) was able to induce a thrombocytosis for following the adenovirus infection; AdRSV␤galactosidase more than 6 weeks in SCID mice, associated with a injected-mice had higher numbers of BFU-E and CFU-GM megakaryocyte (MK) hyperplasia in different organs. A in the marrow than PBS-injected mice. Myelosuppression marrow and spleen fibrosis was observed at 6 weeks. In induced transient immunosuppression responsible for a immunocompetent mice, a single AdRSVhuTPO injection sustained expression and elevation of platelet numbers for led to a moderate and transient thrombocytosis without at least 5 months. These results further suggest that TPO myelofibrosis. To evaluate the usefulness of TPO for the may be an effective therapy in diminishing hematological prevention of secondary side-effects during an aplastic complications related to myeloablative regimens, but period, mice were subjected to a myeloablative regimen 7 emphasize that immunosuppression secondary to myelodays after the intravenous AdRSVhuTPO injection. In this suppression may lead to sustained expression associated setting, TPO prevented mortality by accelerating hematowith a risk of thrombosis and myelofibrosis when delivered logical recovery. Survival was essentially related to by adenovirus vectors.

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“…[1][2][3][4][5][6] MGDF has potent effects on the generation, proliferation and differentiation of megakaryocyte (MK) progenitor cells in vitro and in vivo. [7][8][9][10] Patients treated for acute myelogenous leukemia (AML) who achieved first remission show severe and persistent haematopoietic damage manifested by substantially decreased numbers of clonogenic progenitor cells and of stem cells.…”

Section: Introductionmentioning

confidence: 99%

Recombinant human megakaryocyte growth and development factor (MGDF) increases the numbers of megakaryocyte progenitor cells to normal values in long-term bone marrow cultures of patients with AML in first remission

et al. 1998

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The megakaryopoietic potential in the bone marrow (BM) of patients in first remission after treatment for acute myelogenous leukaemia (AML) was investigated using long-term bone marrow cultures (LTC) stimulated with megakaryocyte growth and development factor (MGDF). The baseline number of megakaryocyte colony-forming cells (Meg-CFC) was very low. However, there was a 10 to 100-fold increase of Meg-CFC in cultures treated with 10 ng/ml MGDF with mean numbers within the normal range for the first 4 weeks of culture with a 24-fold increase in their cumulative numbers. Similarly, a 12-fold increase in the numbers of megakaryocytes (MKs) was found by CD61 immunostaining. These effects were lost at the dose of 100 ng/ml. In contrast, the cumulative mean numbers of Meg-CFC in the control cultures from normal bone marrow (NBM) were not significantly different from those in cultures treated with 10 or 100 ng/ml MGDF. These results demonstrate that MGDF stimulates megakaryocytopoiesis in patients with AML in first remission, restoring the Meg-CFC compartment to normal values, a result with potential clinical implications for their treatment with autologous transplantation.

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Identification and cloning of a megakaryocyte growth and development factor that is a ligand for the cytokine receptor MpI

Cited by 946 publications

References 36 publications

Serum thrombopoietin levels in patients correlate inversely with platelet counts during chemotherapy-induced thrombocytopenia

Serum thrombopoietin levels in patients correlate inversely with platelet counts during chemotherapy-induced thrombocytopenia

Major effects of TPO delivered by a single injection of a recombinant adenovirus on prevention of septicemia and anemia associated with myelosuppression in mice: risk of sustained expression inducing myelofibrosis due to immunosuppression

Recombinant human megakaryocyte growth and development factor (MGDF) increases the numbers of megakaryocyte progenitor cells to normal values in long-term bone marrow cultures of patients with AML in first remission

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