Also ...hematopoiesis

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. 

Cancer patients also may have concurrent iron deficiency secondary to erythropoietin use ( functional iron deficiency) or to cancer. Therefore, it is imperative that these patients have iron studies done to assess adequate iron stores needed to drive hematopoiesis. If the patient is determined to have sub-optimal iron stores or is iron deficient, then replacement either orally or intravenously may be necessary, in addition to the use of erythropoietin products. The use of iron in these patients is the same as discussed previously under Iron-Deficiency Anemia. ... 

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. 

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... 

Beyond roles of chemokine receptors in hematopoiesis and innate immunity, roles for chemokines in adaptive immunity emerged. Moreover, other nonleukocyte migration properties of chemokine receptors have been identified. These include roles in the biology of endothelial cells (Chapter 15), cancer (Chapter 16), smooth muscle (Chapter 11), fibroblasts (Chapter 14), stem cells (Chapter 8), and all cell types associated with nervous system tissues (Chapter 17). In many instances, broad functional overlap is evident as chemokines can direct the migration of these cells just as they do with leukocytes. In certain instances, the ability of chemokines to retain cell populations within a specific microenvironment is as important as their migration-promoting properties. However, it is also clear that migration and retention are not the sole end points. 

In addition to erythrocytes, blood contains white blood cells, called leukocytes, of several types, and platelets, also called thrombocytes, which control blood clotting. Hematopoiesis (from the Greek, haimo, for blood, and poiein for to make ) is the process by which the elements of the blood are formed. The marrow of bone contains so-called stem cells which are immature predecessors of these three types of blood cells. Chemicals that are toxic to bone marrow can lead to anemia (decreased levels of erythrocytes), leukopenia (decreased numbers of leukocytes), or thrombocytopenia. Pancytopenia, a severe form of poisoning, refers to the reduction in circulatory levels of all three elements of the blood. One or more of these conditions can result from sufficiently intense exposure to chemicals such as benzene, arsenic, the explosive trinitrotoluene (TNT), gold, certain drugs, and ionizing radiation. Health consequences can range... 

In conclusion the present report confirms the significant impact of y-retroviral vector insertion sites on the establishment of clonal dominance in hematopoiesis after (serial) bone marrow transplantation. The identification of a number of putative sternness genes may contribute not only to a better understanding of stem cell biology but, in the long run also to the development of novel approaches for stem cell based therapeutic regimens, e.g. in regenerative medicine. 

Numerous case reports and epidemiological studies suggest a leukemogenic action of benzene in humans—the leukemia tending to be acute and myeloblastic in type, often following aplastic changes in the bone marrow. Acute myelocytic leukemia may be preceded by myelodysplastic syndrome, a preleukemic state characterized by abnormal marrow architecture, inadequate hematopoiesis, and many cells with chromosome damage." Benzene may also induce chronic types of leukemia. ... 

Primary or secondary pharmacology can influence hematopoiesis because hematopoietic and stromal cells express many different receptors that are also therapeutic targets, such as neurotransmitters [23-25], In the mouse, an HI receptor agonist antagonized the H2-induced increase of CFU-GM by its off-target effect at the latter receptor [26], Albeit this is not an example of direct hematotoxicity, it does demonstrate that therapeutic drugs bind to targets on hematopoietic and stromal cells and influence hematopoiesis. 

Bone marrow is the natural site of hematopoiesis and was therefore the first source of hematopoietic stem and progenitor cells. In addition to the hematopoietic cells primary stroma can also be collected simultaneously from this source. However, as the harvesting of cells from bone marrow is an invasive procedure that requires manual extraction under spinal or general anesthesia, alternative sources are preferred whenever possible, although, for allogeneic stem cell transplantation, bone marrow is still the source of choice [23]. 

As outhned earUer every single step of hematopoiesis is regulated and controlled in vivo by the cell s microenvironment. This not only includes the composition and concentration of growth factors, but also the local oxygen concentration, the pH, the osmolaHty, the supply of nutrients and the cellular and molecular surrounding of the cells (cell-cell contact, adhesion molecules and extracellular matrix). All these parameters affect the fate of the cell and, to estabUsh a cell culture process to cultivate or generate a specific subpopulation, the influence of all these factors has to be considered in the experimental set-up. In the following sections these parameters will be discussed in brief. 

The regulation of hematopoiesis in the bone marrow is not only controlled by the cytokine composition, the cells microenvironment and the oxygen tension, but, as shown recently [55], also by the local pH. For cells of different Hneages deviating pH optima have been described. While CFU-GM proliferate best in a pH range 7.2 - 7.4 (the normal pH of blood), for erythroid cells an optimum of pH 7.6 was found. Below an acidic pH of 6.7 no differentiation or proUferation of any hematopoietic cell was observed. Cells of the erythroid lineage are even strongly inhibited at a pH below 7.1 [56]. 

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