The molecular mechanisms that control thrombopoiesis.

Department of Medicine, Division of Hematology/Oncology, University of California, San Diego, California 92103-3931, USA.
Journal of Clinical Investigation (Impact Factor: 13.77). 01/2006; 115(12):3339-47. DOI: 10.1172/JCI26674
Source: PubMed

ABSTRACT Our understanding of thrombopoiesis--the formation of blood platelets--has improved greatly in the last decade, with the cloning and characterization of thrombopoietin, the primary regulator of this process. Thrombopoietin affects nearly all aspects of platelet production, from self-renewal and expansion of HSCs, through stimulation of the proliferation of megakaryocyte progenitor cells, to support of the maturation of these cells into platelet-producing cells. The molecular and cellular mechanisms through which thrombopoietin affects platelet production provide new insights into the interplay between intrinsic and extrinsic influences on hematopoiesis and highlight new opportunities to translate basic biology into clinical advances.

1 Follower
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The role of platelets extends beyond hemostasis. The pivotal role of platelets in inflammation has shed new light on the natural history of conditions associated with acute or chronic inflammation. Beyond the preservation of vascular integrity, platelets are essential to tissue homeostasis and platelet-derived products are already used in the clinics. Unanticipated was the role of platelets in the adaptative immune response, allowing a renewed conceptual approach of auto-immune diseases. Platelets are also important players in cancer growth and dissemination. Platelets fulfill most of their functions through the expression of still incompletely characterized membrane-bound or soluble mediators. Among them, CD154 holds a peculiar position, as platelets represent a major source of CD154 and as CD154 contributes to most of these new platelet attributes. Here, we provide an overview of some of the new frontiers that the study of platelet CD154 is opening, in inflammation, tissue homeostasis, immune response, hematopoiesis and cancer.
    03/2015; 4:6. DOI:10.1186/s40164-015-0001-6
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective. To assess the effectiveness of recombinant human thrombopoietin (rhTPO) in severe aplastic anemia (SAA) patients receiving immunosuppressive therapy (IST). Methods. Eighty-eight SAA patients receiving IST from January 2007 to December 2012 were included in this retrospective analysis. Of these, 40 subjects received rhTPO treatment (15000 U, subcutaneously, three times a week). rhTPO treatment was discontinued when the platelet count returned to normal range. Hematologic response, bone marrow megakaryocyte recovery, and time to transfusion independence were compared. Results. Hematologic response was achieved in 42.5%, 62.5%, and 67.5% of patients receiving rhTPO and 22.9%, 41.6%, and 47.9% of patients not receiving rhTPO at 3, 6, and 9 months after treatment, respectively (P = 0.0665, P = 0.0579, and P = 0.0847, resp.). Subjects receiving rhTPO presented an elevated number of megakaryocytes at 3, 6, and 9 months when compared with those without treatment (P = 0.025, P = 0.021, and P = 0.011, resp.). The time to platelet and red blood cell transfusion independence was shorter in patients who received rhTPO than in those without rhTPO treatment. Overall survival rate presented no differences between the two groups. Conclusion. rhTPO could improve hematologic response and promote bone marrow recovery in SAA patients receiving IST.
    01/2015; 2015:1-6. DOI:10.1155/2015/597293
  • [Show abstract] [Hide abstract]
    ABSTRACT: We investigated the exercise and different environmental luminosities effects on blood platelets count in order to identify primary and secondary thrombocytosis, respectively. Platelets alteration has been associated with important pathological events, such as neurodegenerative diseases, and the count of these cells in bloodstream is influenced by several effects, including physical and chemical. Owing the difficulty to study the aetiology of thrombocytosis in human models, we employed acute and chronic free drug interventions in order to identify these two types of this important disease in laboratory animals. Forty rats were exposed to standard (SI) or experimental (EI) illumination from 45 days-old. Both groups were exposed to 12 h daylight (2700 K; 565-590 nm; < 60 lux; from 06:00 h to 18:00 h). During dark period SI animals were kept in total darkness while EI remained under red light (> 600 nm, < 15 lux). At 92 days-old, exercised animals were submitted to an acute bout of swimming at individualized intensity and control animals remained at rest. Blood samples were collected immediately after the exercise for platelets count, which were among 849000 ± 115817 and 1085600 ± 177089/mm³ of blood. Exercise (F = 6.91; p = 0.01) and EI (F = 6.66; p = 0.01) increased platelets count, showing no interaction between effects (F = 0.01; p = 0.89). Primary thrombocytosis was detected owing an acute exercise and the secondary thrombocytosis due to the constant red light during dark period, without any pharmacological interventions and strongly respecting the ethical aspects, enabling future studies on aetiology of thrombocytosis through this model (Fig. 2, Ref. 35). thrombocytosis, platelets, exercise, animal model, environmental luminosity.
    Bratislavske lekarske listy 01/2014; 115(10):607-10. DOI:10.4149/BLL_2014_117 · 0.45 Impact Factor


Available from