The control of growth and differentiation in normal and leukemic blood cells
Article Abstract:
The author, a pioneer in the discovery of hematopoietic growth factors, describes his research on the class of proteins now called colony-stimulating factors. These factors were first identified in cells cultured in dishes with agar. The molecular meshwork of the gelatin-like agar permits small proteins to diffuse freely, but cells, being so much larger, are held in place. Therefore, it is possible to observe the interactions of different cells which are not in actual contact. Colony-stimulating factors were observed by virtue of their ability to cause visible clusters of the target cells, generally granulocytes or macrophages (two types of white blood cell). Since the cells cannot move, a cluster represents a "colony" formed by a progenitor cell which has been stimulated to multiply. In addition to the factors which stimulate growth, there are also factors which induce differentiation. That is, they stimulate cells to express those mature characteristics which distinguish adult cell types from one another. One such factor is interleukin-6 (IL-6). Experiments in mice have shown that factors such as IL-6 which induce differentiation in normal cells can also induce differentiation in some leukemic cells. In general, the expression of mature, differentiated characteristics seems to be incompatible with cell proliferation. Therefore, at the same time that a cell is being stimulated to express mature characteristics, it is also being stimulated to stop dividing. Thus differentiation- inducing substances such as IL-6 may prove to be of some value in the treatment of leukemia. This prospect is especially interesting considering the serious toxicities associated with conventional chemotherapy. The hematopoietic growth factors may play yet another role in cancer therapy. In many cases, the dose-limiting factor for anti-cancer drugs is the adverse effect of myelosuppression, or destruction of bone marrow cells. Since these cells are critical for the defense against infection, chemotherapy must sometimes be terminated if myelosuppression becomes severe. It may become possible to use hematopoietic growth factors for stimulating remaining bone marrow cells to produce the necessary cells for immune defenses. Hematopoietic growth factors may speed up the recovery process of bone marrow, thus not only protecting the patient from infection, but perhaps also permitting the use of larger and more effective doses of anti-cancer drugs. (Consumer Summary produced by Reliance Medical Information, Inc.)
Publication Name: Cancer
Subject: Health
ISSN: 0008-543X
Year: 1991
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Acute respiratory failure and pulmonary thrombosis in leukemic children
Article Abstract:
Pulmonary complications are not uncommon among patients receiving chemotherapy. Most often, these complications are a result of infections following immunosuppression (suppression of the immune system), which occurs with chemotherapy. However, a case was recently reported in which an 11-year-old child with leukemia died as a result of respiratory insufficiency due to thrombosis (the formation of a blood clot) blocking the pulmonary circulation. The chest X-rays of the patient appeared entirely normal, and by the time the nature of the respiratory insufficiency was recognized, the use of thrombolytic enzymes to dissolve the offending clot was insufficient to save the patient. This case alerted clinicians to the possibility of pulmonary thrombosis as a complication of chemotherapy in children. Subsequently, clinicians identified six more children with the condition, indicating that pulmonary insufficiency resulting from pulmonary thrombosis may be more common than has been previously suspected. All seven patients were undergoing chemotherapy for acute leukemia, lymphoblastic in two cases and nonlymphoblastic in five. The presence of thromboemboli (fragments of clotted tissue obstructing vessels) in the pulmonary arteries of the patients was confirmed using angiography (an X-ray technique). Six of the patients were successfully treated with the thrombolytic enzyme urokinase, and in all but one patient angiography was also used to confirm the dissolution of the clot. As might be expected, the damage to the lungs in these seven cases was related to the time of diagnosis; patients diagnosed earlier had a single clot in a large arterial vessel. It is presumed that later diagnosis is a primary risk factor associated with the obstruction of multiple arteries. The cause of the thromboemboli is not known, but theory is that tiny neoplastic emboli, which result from the destruction of cancer cells by the chemotherapeutic agents, may serve to provoke the blood coagulation. (Consumer Summary produced by Reliance Medical Information, Inc.)
Publication Name: Cancer
Subject: Health
ISSN: 0008-543X
Year: 1991
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