Erythrocytes precursor cells

On a more cautionary note, the EPO receptor is expressed not only by specific erythrocyte precursor cells, but also by endothelial, neural, and myeloma cells. Concern has been expressed that EPO, therefore, might actually stimulate growth of some tumour types, particularly those derived from such cells. To date, no evidence (in vitro or in vivo) has been obtained to support this hypothesis. 

The magnitude of these losses emphasises the importance of regulating the amount of iron in cells, especially in those cells in which it plays a key role erythrocyte precursor cells and proliferating cells. Three proteins are involved in the regulation of the iron concentration in a cell ... 

Erythropoietin release is stimulated by hypoxia (low PO2). Within hours, the hormone ensures that erythrocyte precursor cells in the bone marrow are converted to erythrocytes, so that their numbers in the blood increase. Renal damage leads to reduced erythropoietin release, which in turn results in anemia. Forms of anemia with renal causes can now be successfully treated using erythropoietin produced by genetic engineering techniques. The hormone is also administered to dialysis patients. Among athletes and sports professionals, there have been repeated cases of erythropoietin being misused for doping purposes. 

The underlying rationale still being similar - specific immune reactions strongly depend on cell (lymphocyte) proliferation. Folic acid is a vitamin, and a lack of this vitamin gives rise to anemia. There are fewer erythrocytes in this condition, but those present have a higher than normal hemoglobin content. Synthesis of proteins is not inhibited, and the erythrocyte precursor cells accumulate more protein because they divide less rapidly. 

Erythropoietin is a potent stimulator of growth and differentiation of erythroblasts, erythrocyte precursor cells. 

Hemolysis, if sufficiently severe, produces an LD isoenzyme pattern similar to that in myocardial infarction. Megaloblastic anemias, usually resulting from the deficiency of folate or vitamin cause the erythrocyte precursor cell to break down in the bone marrow (ineffective erythropoiesis), resulting in the release of large quantities of LD-1 and LD-2 isoenzymes. Marked elevations of the total LD activity in serum— up to 50 times the upper reference limit—have been observed in the megaloblastic anemias. These elevations rapidly return to normal after appropriate treatment. 

The erythrocyte precursor cell types display a continuum of changes in shape, hemoglobin concentration, Rh antigen, and erythropoietin (EPO) receptor expression with maturity. However, mature erythrocytes express significantly lower EPO receptor density than do proerythroblasts. ... 

In addition to fully differentiated cells, many tissues of the body contain stem cells - precursor cells that are not fully differentiated. These can divide to produce more stem cells but can also give rise to progeny which can differentiate. Stem cells in the bone marrow, for example, give rise to all the different types of immune cells, erythrocytes and megakaryocytes, which give rise to platelets. 

The anaemia in B deficiency is caused by an inability to produce sufficient of the methylating agent S-adenosyhnethionine. This is required by proliferating cells for methyl group transfer, needed for synthesis of the deoxythymidine nucleotide for DNA synthesis (see below and Chapter 20). This leads to failure of the development of the nucleus in the precursor cells for erythrocytes. The neuropathy, which affects peripheral nerves as well as those in the brain, is probably due to lack of methionine for methyl transfer to form choline from ethanolamine, which is required for synthesis of phosphoglycerides and sphingomyelin which are required for formation of myelin and cell membranes. Hence, the neuropathy results from a... 

Erythropoetin EPO kidney erythroid cells (erythrocyte precursors) ... 

Except for lymphocytes, each specialized blood cell Is a workhorse at the end of its road each remains in the circulatory system or In a tissue and then dies, perhaps as a result of doing its job. Red ceiis (erythrocytes) have lost their nucleus, and platelets are fragments of precursor cells. Because they have no nuclei, human red cells and platelets cannot divide. 

Schematic representation of the hematopoietic cascade in mice and human (hum). All the cells of the hematopoietic system are positive for antigen CD45. Based on this, the dynamics of surface antigen expression along development of different mature cells derived from the hematopoietic stem cell system can be observed. Rounded arrows indicate self-renewal potential. Smooth thinner arrows indicate directions of cellular differentiation. The identification of CDs (clusters definition) and other antigen cell markers are listed in the glossary. (LT-HSC - long term hematopoietic stem cell ST-HSC - short term hematopoietic stem cell MPP - multipotent progenitor CLP - common lymphoid precursor CMP - common myeloid precursor GMP - granulocyte-monocyte precursor MEP - megacaryocyte-erythrocyte precursor T - T lymphocyte B - B lymphocyte NK - natural killer cell DC - dendritic cell).

Human erythropoietin (hEpo) is a glycoprotein of 36,000 daltons, produced by the kidney in response to hypoxia. It regulates the rate of production of mature erythrocytes by stimulating the proliferation and differentiation of erythroid precursor cells. Renal failure leads to lack of this growth factor which, in turn, leads to anemia (Hillman, 1990 Cotes and Spivak, 1991). 

Erythropoietin is a glycoprotein hormone encoded by a gene on the long arm of chromosome 7 (7q) and 90% is produced in the kidney (the remainder in the liver and other sites) in response to hypoxia. The anaemia of chronic renal failure is largely due to failure of the diseased kidneys to make enough erythropoietin. The principal action of the hormone is to stimulate the proliferation, survival and differentiation of erythrocyte precursors. The manufacture of erythropoietin for clinical use became possible when the human gene was successfully inserted into cultured hamster ovary cells. 

Radiophosphorus ( P, sodium radiophosphate) is given i.v. Phosphorus is concentrated in bone and in cells that are dividing rapidly, so that the erythrocyte precursors in the bone marrow receive most of the P-irradiation. The effects are similar to those of whole-body irradiation, and in PRV, P is a treatment option for those > 65 years (acaunulation in the gonads precludes its use in younger patients). The maximum effect on the blood count is delayed 1-2 months after a single dose that usually provides control for 1-2 years. It reduces vascular events and delays progression to myelofibrosis. Excessive depression of the bone marrow including leucocytes and platelets is the main adverse effect, but is seldom serious. Acute myeloid leukaemia occurs more frequently in patients treated with P especially when used in combination with hydroxyurea. 

The hormone EPO, 90% of which is produced by the kidneys, initiates and stimulates the production of RBCs. Erythropoiesis is driven by a feedback loop. The main mechanism of action of EPO is to prevent apoptosis, or programmed cell death, of erythroid precursor cells and to allow their proliferation and subsequent maturation. A decrease in tissue oxygen concentration signals the kidneys to increase the production and release of EPO into the plasma, which (1) stimulates stem cells to differentiate into proerythroblasts, (2) increases the rate of mitosis, (3) increases the release of reticulocytes from the marrow, and (4) induces Hgb formation. In normal circumstances, the RBC mass is kept at an almost constant level by EPO matching new erythrocyte production to the namral rate of loss of RBCs. Accelerated Hgb synthesis makes it possible to achieve the critical Hgb concentration necessary for RBCs to mature more rapidly, and a feedback mechanism stops further RBC nucleic acid synthesis, causing an earlier release of reticulocytes. Early appearance of large quantities of reticulocytes in the peripheral circulation (reticulocytosis) is another indication of increased RBC production. 

The hematopoietic lineage originally was worked out by Injecting the various types of precursor cells into mice whose precursor cells had been wiped out by irradiation. By observing which blood cells were restored in these transplant experiments, researchers could infer which precursors or terminally differentiated cells (e.g., erythrocytes, monocytes) arise from a particular type of precursor. The first step in these experiments was separation of the different types of hematopoietic precursors. This is possible because each type produces unique combinations of cell-surface proteins that can serve as type-specific markers. If bone marrow extracts are treated with fluorochrome-labeled antibodies for these markers, cells with different surface markers can be separated in a fluorescence-activated cell sorter (see Figure 5-34). 

In order for most oncogenic mutations to induce cancer, they must occur in dividing cells so that the mutation is passed on to many progeny cells. When such mutations occur in nondividing cells (e.g., neurons and muscle cells), they generally do not induce cancer, which is why tumors of muscle and nerve cells are rare in adults. Nonetheless, cancer can occur in tissues composed mainly of nondividing differentiated cells such as erythrocytes and most white blood cells, absorptive cells that line the small Intestine, and keratinized cells that form the skin. The cells that Initiate the tumors are not the differentiated cells, but rather their precursor cells. Fully differentiated cells usually do not divide. As they die or wear out, they are continually replaced by proliferation and differentiation of stem cells, and these cells are capable of transforming Into tumor cells. 

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