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

One of the clinical features of chronic myeloid leukemia (CML) after splenectomy lies in the development of an unusual hyperthrombocytic syndrome. In the course of a long-term observation, 12 out of 14 patients subjected to splenectomy demonstrated maximum thrombocytosis ranging from 1.008 X 10(9) to 3.053 X 10(9)/l. Hemorrhagic manifestations occurred in 6 patients, no thromboses were recorded. Postsplenectomy hyperthrombocytosis is to a certain measure resistant to cytostatic therapy. Dissociation may occur--good readings of the leukogram with a high hyperthrombocytosis. According to the authors' and reported data, the postsplenectomy hyperthrombocytic syndrome in ALL patients is fraught with the danger of the occurrence of hemorrhagic manifestations and, to a less degree, of thromboses.
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PMID:[The characteristics of the postsplenectomy hyperthrombocytic syndrome in patients with chronic myeloleukemia]. 178 10

Several inhibitors of the arachidonic acid-metabolizing enzyme, 5-lipoxygenase reduce proliferation of hematopoietic and non-hematopoietic cells and cell lines and some cells undergo limited differentiation. Cells were cultured from patients with chronic myelogenous leukemia in "blast" crisis with the selective inhibitor of 5-lipoxygenase, SC41661A[3-(3,5-bis(1,1-dimethyl)-4-hydroxyphenyl)hiol]-N-me thyl-N-[2-(2- phridinyl-propanamide)]. Cells cultured for 3 to 5 days with 40 microM SC41661A exhibited reduced cellular numbers along with ultrastructural changes and DNA laddering characteristic of apoptosis. Similar culture conditions reduced proliferation of U937 monoblastoid cells. In U937 cells, the ultrastructural features of apoptosis were not observed at 72 hours, when DNA laddering was present and cell numbers were reduced, but was present after 144 hours of culture. Dissociation between certain morphologic and biochemical sequelae of apoptosis has been described in other systems. These observations are of interest since the induction of apoptosis in dividing chronic myelogenous leukemia (CML) cells by a non-cytotoxic agent suggests paradigmatically new sites for therapeutic intervention.
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PMID:Morphologic changes of apoptosis induced in human chronic myelogenous leukemia "blast" cells by SC41661A (Searle), a selective inhibitor of 5-lipoxygenase. 774 66

Acute promyelocytic leukemia (APL) is characterized by a specific chromosome translocation involving RARalpha and one of four fusion partners: PML, PLZF, NPM, and NuMA genes. To study the leukemogenic potential of the fusion genes in vivo, we generated transgenic mice with PLZF-RARalpha and NPM-RARalpha. PLZF-RARalpha transgenic animals developed chronic myeloid leukemia-like phenotypes at an early stage of life (within 3 months in five of six mice), whereas three NPM-RARalpha transgenic mice showed a spectrum of phenotypes from typical APL to chronic myeloid leukemia relatively late in life (from 12 to 15 months). In contrast to bone marrow cells from PLZF-RARalpha transgenic mice, those from NPM-RARalpha transgenic mice could be induced to differentiate by all-trans-retinoic acid (ATRA). We also studied RARE binding properties and interactions between nuclear corepressor SMRT and various fusion proteins in response to ATRA. Dissociation of SMRT from different receptors was observed at ATRA concentrations of 0.01 microM, 0.1 microM, and 1.0 microM for RARalpha-RXRalpha, NPM-RARalpha, and PML-RARalpha, respectively, but not observed for PLZF-RARalpha even in the presence of 10 microM ATRA. We also determined the expression of the tissue factor gene in transgenic mice, which was detected only in bone marrow cells of mice expressing the fusion genes. These data clearly establish the leukemogenic role of PLZF-RARalpha and NPM-RARalpha and the importance of fusion receptor/corepressor interactions in the pathogenesis as well as in determining different clinical phenotypes of APL.
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PMID:Distinct leukemia phenotypes in transgenic mice and different corepressor interactions generated by promyelocytic leukemia variant fusion genes PLZF-RARalpha and NPM-RARalpha. 1033 85