Browsing by Subject "Hematopoiesis"

Now showing 1 - 6 of 6
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    Intrinsic and extrinsic regulation of mammalian hematopoiesis in the fetal liver
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2014) Swain, Anthony; Inoue, Tomoko; Tan, Keai Sinn; Nakanishi, Yoichi; Sugiyama, Daisuke
    The fetal liver (FL) is an important structure in expansion and differentiation of hematopoietic stem cells (HSC), but despite this little is known about the exact mechanisms in which FL hematopoiesis takes place. Primitive hematopoiesis gives way to definitive hematopoiesis at 12.5 dpc in mice and the process is regulated by a number of intrinsic and extrinsic factors. Intrinsic regulations are intracellular processes that have been reported to be important in the initiation of definitive hematopoiesis. Several structures are involved with extrinsic regulations of hematopoiesis within the FL, including hepatoblasts and liver sinusoidal endothelial cells (LSEC). Hepatoblasts and endothelial cells comprise separate niches involved in the extrinsic regulation of hematopoiesis. Studies have shown that cocultures with fetal liver stromal cells can promote the expansion of erythroid cells, although the way in which stromal cells do this is still unknown. Understanding the mechanisms in which hematopoiesis is regulated in the FL could lead to the production of novel therapies involving the safe and reliable transplantation of HSCs to patients with blood and bone marrow complications. This review aims to summarize the current state of knowledge about the regulation of hematopoiesis specifically within the FL.
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    Is hematopoiesis under the influence of neural and neuroendocrine mechanisms?
    (Murcia : F. Hernández, 1998) Maestroni, G.J.M.
    It is well recognized that the immune response is under the influence of a variety of neural or neuroendocrine mechanisms. Much less studied is the possible influence of these mechanisms on hematopoiesis. Here I review the existing evidence about a neural andlor neuroendocrine regulation of hematopoiesis. The physiology of the blood forming system seems to be controlled at three levels, i.e. at the cellular level by the bone marrow stroma, at the humoral level by hematopoietic cytokines and finally by catecholamines and neuroendocrine factors. Bone marrow catecholarnines originate from sympathetic nerve fibers and from hematopoietic cells directly. Catecholamines of neural origin show a circadian rhythmicity. Adrenoceptors present on bone marrow cells include the a l - subtype which seems to mediate the catecholaminergic control of hematopoiesis. Neuroendocrine factors including substance P, neurokinin-A and the pineal hormone melatonin might also influence hematopoiesis by affecting hernatopoietic cytokines. In particular, melatonin seems to affect hematopoiesis via the induction in bone marrow T-helper cells of two novel opioid cytokines. A complete understanding of the neural and neuroendocrine regulation of hematopoiesis might provide new conceptual and therapeutic perspectives in a variety of hematopoietic and immune diseases.
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    Regulation mechanisms for the heterodimeric transcription factor, PEBP2lCBF
    (Murcia : F. Hernández, 1999) Bae, S.C.; Ito, Y.
    Members of the new PEBP2 (Polyomavirus Enhancer Binding Protein 2) family of heterodimeric transcriptional regulatory protein are composed of two subunits, a and B. One of the genes encoding the a subunit, AMLlIPEBP2aB, was identified at the breakpoints of various chromosome translocations, including t(8;21) and t(12;21) associated with acute myeloid leukemia and acute lymphoblastic leukemia, respectively. The gene encoding the B subunit (PEBP2flCBFB) was also shown to be the target of the inversion of chromosome 16, another chromosomal anomaly associated with acute myeloid leukemia. Targeted disruption of either the AmlllPebp2aB or PebpZflICbfb gene resulted in strikingly similar phenotypes such as lack of definitive hematopoiesis of the fetal liver and accompanying hemorrhage of the central nervous system. These observations suggest that both a and l3 subunits of PEBP2 are indispensable for its in vivo function. However, the heterodimerization of the a and B subunit does not seem to occur readily suggesting that their capacity to associate might be an important rate limiting step in PEBP2 site-dependent transcription regulation. In this review, we concentrate on the possible regulatory mechanisms of PEBP2 activity in relation to leukemogenesis.
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    Role of WNT signaling in normal and malignant hematopoiesis
    (Murcia : F. Hernández, 2006) Khan, N.I.; Bendall, L.
    The WNT pathway is a powerful signaling pathway that plays a crucial role in cell fate determination, survival, proliferation and movement in variety of tissues. Abnormalities in the WNT signaling pathway have been implicated in a number of diseases, most notably cancer. Recent exciting evidence suggests that WNT signaling also plays an important role in hematopoietic stem cell self-renewal and progenitor development. In this review we discuss current state of knowledge on WNT signaling in hematopoiesis and extend our focus on aberrant WNT signaling in hematological malignancies.
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    SDF-1 and CXCR4 in normal and malignant hematopoiesis
    (Murcia : F. Hernández, 2004) Juarez, J.; Bendall, L.
    Over recent years it has become apparent that the chemokine SDF-1 and its receptor CXCR4 play pivotal roles in normal hematopoiesis. They are essential for the normal ontogeny of hematopoiesis during embryogenesis and continue to play a key role in retaining hematopoietic progenitors within the bone marrow microenvironment in the adult. As a result of this role disruption of SDF-1/CXCR4 interactions results in mobilization of hematopoietic progenitors and standard mobilization protocols disrupt this axis. Similarly SDF-1/CXCR4 interactions are required for homing and engraftment of hematopoietic stem cells during transplantation. SDF-1 regulates the localisation of leukemic cells and like their normal counterparts most leukemic cells respond to SDF-1 with increased adhesion, survival and proliferation. However in some instances leukemic cell responses to SDF-1 can be disregulated, the impact of which on the progression of disease in not known. In this review we discuss the pleiotropic roles of SDF-1/CXCR4 interactions in human hematopoietic stem cell ontogeny, bone marrow homing and engraftment, mobilization and how these interactions impact on malignant hematopoiesis.
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    The phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin signaling network and the control of normal myelopoiesis
    (Murcia : F. Hernández, 2010) Martelli, Alberto M.; Chiarini, Francesca; Evangelisti, Camila; Grimaldi, Cecilia; Ognibene, Andrea; Manzoli, Lucia; Billi, A.M.; McCubrey, James A.
    he phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway plays a central role in cell growth, proliferation, differentiation, and survival under physiological conditions. Aberrant regulation of the PI3K/Akt/mTOR signal transduction network has been observed in a wide range of neoplasias, including malignant hematological disorders. This observation suggests that this signaling cascade could also play a critical role during normal hematopoiesis, a highly regulated process which results in the formation of all blood lineages. The development of blood cells comprises a complex series of events which are mainly regulated through the actions of cytokines, a large family of extracellular ligands than can stimulate many biological responses in a wide array of cell types. Several of these cytokines are known to activate the PI3K/Akt/mTOR signal transduction network and thus regulate proliferation, survival, and differentiation events during hematopoiesis. Moreover, hematopoiesis is strictly dependent on the correct functions of the bone marrow microenvironment. Here, we review the evidence which links the signals emanating from the PI3K/Akt/mTOR cascade with the functions of hematopoietic stem cells and the process of lineage commitment, which then gives rise to myeloid lineage-restricted cells. We then further highlight the key role played by the PI3K/Akt/mTOR network during erythropoiesis, megakaryocytopoiesis, and granulo-cytopoiesis/monocytopoiesis