Bone marrow hematopoiesis

Chemotherapeutic agents for cancer therapy are sometimes subjected to a limit of use because of the adverse effects. One of the critical adverse effects is leukopenia induced by a suppression of bone marrow hematopoiesis resulting in opportunistic infections. In this regard, an improvement of impaired hematopoiesis is required to obtain a satisfactory outcome in the cancer chemotherapy. 

Spleen weight effects, spleen congestion, spleen and bone marrow hematopoiesis, and hemosiderin pigmentation in the spleen are probably related to hemolytic effects of 2-butoxyethanol, which are discussed in Section 2.2.2.2 under Hematological Effects. 

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... 

Flow cytometric evaluation of bone marrow and peripheral blood to characterize the type of leukemia, as well as to detect specific chromosomal rearrangements. The bone marrow at diagnosis usually is hypercellular, with normal hematopoiesis being replaced by leukemic blasts. The presence of greater than 20% blasts in the bone marrow is diagnostic for AML. 

The cellular elements of the blood have a short life span and must be continuously replaced. The formation of red blood cells, white blood cells, and platelets, collectively, is referred to as hematopoiesis. This process takes place in the red bone marrow. In adults, red bone marrow is found in the pelvis, ribs, and sternum. 

Bone marrow becomes the major site of hematopoiesis — 2228 — 17.515-76... 

Bone marrow becomes major site for hematopoiesis... 

Morioka, Y., et al. Immunophenotypic and ultrastructural heterogeneity of macrophage differentiation in bone marrow and fetal hematopoiesis of mouse in vitro and in vivo, J. Leukoc. Biol., 55, 642, 1994. 

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. 

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. 

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. ... 

Continuous exposure of rats by inhalation to 0.0055 and 0.3mg/m for 100 days resulted in methemoglobinemia, lowered erythrocyte hemoglobin, leukopenia and reticulocytosis, and reduced muscle chronaxie. Doses up to 500mg/kg administered by gavage to rats and mice for 13 weeks caused cyanosis and decreased motor activity, as well as hemosiderosis in the spleen liver, kidney, and testes. Bone marrow hyperplasia was observed in rats, and mice had increased hematopoiesis in the liver. In general, all toxic effects could be attributed to chronic methemoglobinemia, erythrocyte destruction, and erythrophagocytosis. 

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