Hematopoietic Hematopoiesis

Deficiency. Macrocytic anemia, megaloblastic anemia, and neurological symptoms characterize vitamin B 2 deficiency. Alterations in hematopoiesis occur because of the high requirement for vitamin B 2 for normal DNA repHcation necessary to sustain the rapid turnover of the erythrocytes. Abnormal DNA repHcation secondary to vitamin B 2 deficiency produces a defect in the nuclear maturational process of committed hematopoietic stem cells. As a result, the erythrocytes are either morphologically abnormal or die during development. 

Hematopoietic (blood) cells transport oxygen and carbon dioxide, contribute to host immunity, and facilitate blood clotting [1], A complex, interrelated, and multistep process, called hematopoiesis, controls the production as well as the development of specific marrow cells from immature precursor cells to functional mature blood cells. This well-regulated process also allows for replacement of cells lost through daily physiologic activities. The proliferation of precursor cells, the maturation of these into mature cells, and the survival of hematopoietic cells require the presence of specific growth factors. 

Hematopoietic Growth Factors. Figure 1 Schema of hematopoiesis, including some of the growth factors that influence the production of blood cells. 

O The acute leukemias are hematologic malignancies of bone marrow precursors characterized by excessive production of immature hematopoietic cells. This proliferation results in a large number of immature cells (blasts) appearing in the peripheral blood and bone marrow causing failure of normal hematopoiesis. 

O The acute leukemias are diseases of bone marrow resulting from aberrant proliferation of hematopoietic precursors. The hallmark of these malignancies is the leukemic blast cell, a visibly immature and abnormal cell in the peripheral blood that often replaces the bone marrow and interferes with normal hematopoiesis. These blast cells proliferate in the marrow and inhibit normal cellular elements, resulting in anemia, neutropenia, and thrombocytopenia. Leukemia also may infiltrate other organs, including the liver, spleen, bone, skin, lymph nodes, and central nervous system (CNS). Virtually anywhere there is blood flow, the potential for extramedullary (outside the bone marrow) leukemia exists. 

Hematopoiesis is defined as the development and maturation of blood cells and their precursors. In utero, hematopoiesis may occur in the liver, spleen, and bone marrow. However, after birth, it occurs exclusively in the bone marrow. All blood cells are generated from a common hematopoietic precursor, or stem cell. These stem cells are self-renewing and pluripotent and thus are able to commit to any one of the different lines of maturation that give rise to platelet-producing megakaryocytes, lymphoid, erythroid, and myeloid cells. The myeloid cell line produces monocytes, basophils, neutrophils, and eosinophils, whereas the lymphoid stem cell differentiates to form circulating B and T lymphocytes. In contrast to the ordered development of normal cells, the development of leukemia seems to represent an arrest in differentiation at an early phase in the continuum of stem cell to mature cell.1... 

A delicate balance between host and donor effector cells is necessary, and residual host-versus-graft effects may lead to graft failure, which is also known as graft rejection. Graft failure is defined as the lack of functional hematopoiesis after HCT and can occur early (i.e., lack of initial hematopoietic... 

Chemokines in Trafficking of Hematopoietic Stem and Progenitor Cells and Hematopoiesis... 

Dudek AZ, Nesmelova I, Mayo K, Verfaillie CM, Pitchford S, Slungaard A. Platelet factor 4 promotes adhesion of hematopoietic progenitor cells and binds IL-8 novel mechanisms for modulation of hematopoiesis. Blood 2003 101(12) 4687-4694. 

The effects of Li+ upon hematopoiesis have been proposed to be due to two different systems modification of the activity of the membrane Na+/K+-ATPase, and the inhibition of adenylate cyclase. Monovalent cation flux, in particular Na+ transport, is known to influence the differentiation and proliferation of hematopoietic stem cells. For instance, ouabain, an effective inhibitor of the membrane Na+/K+-ATPase, blocks the proliferation of lymphocytes and has been shown to attenuate the Li+-induced proliferation of granulocyte precursors [208]. Conversely, Li+ can reverse the actions of amphotericin and monensin, which mediate Na+ transport and which inhibit CFU-GM, CFU-E, and CFU-MK colony formation in the absence of Li+ [209]. Therefore, the influence of Li+ upon normal physiological cation transport—for example, its influence upon Na+/K+-ATPase activity—may be partly responsible for the observed interference in hematopoiesis. 

An important stromal derived growth factor, SCF, appears to play a major role in mechanisms like this. SCF can be expressed as a membrane-bound molecule that can be subsequently cleaved to soluble protein. The physiological functions of these isoforms are not well known. The deficiencies in mature eythroid precursors and in pluripotent hematopoietic stem cells in SI mutant mice (McCulloch et al, 1965) indicated that the membrane-bound SCF isoform has an essential function in hematopoiesis. 

Drize NJ, Keller JR, Chertkov JL. Local clonal analysis of the hematopoietic system shows that multiple small short living clones maintain life long hematopoiesis in reconstituted mice. Blood. 1996 88 2927 2938. 

Abstract. G-CSF Is a major extracellular regulator of hematopoiesis and the most used cytokine in clinical practice. Coherently with and for a long time after the repeated injections of low doses of G-CSF the study of alterations in hematopoietic precursor cells concentration in the bone marrow of mice was undertaken. G-CSF treatment did not affect the number of granulocytes and oligopotent precursor cells (CFU-C). However, frequency of early multipotent stem cells (LTC-IC) decreased one month after the last (7 ) course of G-CSF injections, moreover it halved during the following year. The exhaustion of LTC-IC after G-CSF treatment is discussed. 

Drize N, Chertkov J, Samoilina N et al. Effect of c 4okine treatment (granuloc34e colony-stimulating factor and stem cell factor) on hematopoiesis and the circulating pool of hematopoietic stem cells in mice. Exp Hematol. 1996 24 816-822. 

Okuda, T., Cai, Z., Yang, S., Lenny, N., Lyu, C., van Deursen, J., Harada, H. and Downing, J. (1998) Expression of a knocked-in AMLl-ETO leukemia gene inhibits the establishment of normal definitive hematopoiesis and directly generates dysplastic hematopoietic progenitors. 

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