Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors describe a coherent model for differentiated leukemias derived from physiopathological studies on Friend leukemia. In Friend leukemia, Friend virus induces permanent differentiation of erythropoietin-responsive cells. This erythropoietic proliferation and maturation is accompanied by a marked cell loss and provokes enlargement of the stem cell compartment. The so-called leukemic cells have a limited proliferation capacity and may not be truly malignant as opposed to blastic cells in acute leukemias. Clinical, hematological, and physiopathological data that are presently available in chronic granulocytic leukemia, polycythemia vera, and the erythroblastic component of erythroleukemia are compatible with the Friend physiopathological model. It is suggested that these differentiated leukemias initiate from an uncontrolled differentiation of a committed cell compartment, which stimulates proliferation of the stem cell compartment. The disease would be due to a proliferation and accumulation of "subnormal" cells characterized by a shorter mean life-span than the normal differentiated cell population. Although limited, the data available suggest that the physiopathology of acute leukemias is clearly distinguishable from that of differentiated leukemias; several immunological and therapeutic applications of this model are outlined.
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PMID:Physiopathology of human and virus-induced murine leukemias. 17 21

Specific inhibitors of protein kinase C (PKC) were screened for with a unique detection system, named bleb forming assay. When K562, a human chronic myeloid leukemia cell, was treated with phorbol 12,13-dibutylate (PDBu) or teleocidin which are activators of PKC, many blebs appeared on the cell surface of K562 within 10 minutes. This appearance of blebs is inhibited by staurosporine and H7 which are known to be PKC inhibitors. Teleocidin and PDBu did not induce bleb formation of HL60, a human acute promyelocytic leukemia cell, and the mouse Friend leukemia cell, even though their morphology was changed 24 hours after treatment with teleocidin or PDBu. Many inducers of terminal differentiation of K562 have the same effect on HL60 and Friend cells. However, the bleb inducing activity of PKC activators seems to be specific for K562. The bleb forming assay satisfied the criteria (simplicity and specificity) required for preliminary screening of activators or inhibitors of PKC. Teleocidins A and B, and tautomycin (a new antibiotic isolated in our laboratory) were identified as activators of PKC, and also staurosporine and isoflavones (daidzein and genistein) as inhibitors.
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PMID:Rapid screening method for inhibitors of protein kinase C. 313 26

Clinical studies have indicated that folate deficiency may enhance the development of various malignancies. In animal studies that examined the effect of folate deficiency on malignancies, conflicting results have been reported. In some studies, folate deficiency increased the development and growth of malignant tumors; in others, it decreased the development and growth of malignancies. We examined the effect of transient folate deficiency on the development of leukemia in mice infected with the anemia-inducing strain of Friend leukemia virus. Friend virus disease can be considered as a model for human acute leukemias that are preceded by a preleukemic period. These include leukemias that develop in patients who received previous chemotherapy and/or radiation therapy, as well as patients with chronic granulocytic leukemia or myelodysplasia. Folate deficiency around the time of Friend virus-infection delayed the onset but increased the incidence of leukemia. The rates of rearrangement of the Spi-1 (PU.1 ) oncogene by provirus integration and alteration of the p53 tumor-suppressor gene were the same in leukemia cell lines derived from folate-deficient mice as they were in cell lines from control mice. These results indicate that folate deficiency did not exert its enhancement of leukemogenesis through changes in either Spi-1 or p53, even though these two genes have been found to be the most frequently altered ones in Friend virus-induced leukemias. Our results suggest that folate deficiency may enhance the development of acute leukemia in patients who are at high risk for this disease.
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PMID:Folate deficiency delays the onset but increases the incidence of leukemia in Friend virus-infected mice. 935 75

H-2 antigen variants, derived from a heterozygous mouse Friend leukemia cell line by selection with anti-H-2 antisera and complement, were tested for susceptibility to cell-mediated cytolysis, using T-lymphocytes directed against individual H-2 antigens. The cytotoxic cells were generated in the BALB and B10 backgrounds by a combination of in vivo and in vitro immunizations. The phenotypes of the variants inferred from the patterns of resistance or susceptibility to CML were consistent with those presumed from earlier assays using antisera. The one exception was the variant cell line which was H-2D(d-) in assays using antisera, but was H-2D(d+) by CML.
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PMID:H-2 Antigen variants in a cultured heterozygous mouse leukemia cell line : IV. Cell-Mediated cytolysis of wild type and variant cells. 2130 99