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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
15
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pubmed:dateCreated |
1991-8-28
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pubmed:abstractText |
The discovery of isozymes (types I and II) of IMP dehydrogenase (IMPDH; EC 1.1.1.205), the rate-limiting enzyme of de novo GTP biosynthesis, has attracted attention as a possible novel approach to cancer diagnosis and selective tumor cell chemotherapy. To elucidate differences in expression and regulation of the two IMPDH isozymes, we examined the steady-state levels of these mRNAs in various types of leukemic cells from patients. Northern blot analysis revealed that type II IMPDH was more active transcriptionally (1.5- to 5.1-fold) in all the leukemic cells examined than in normal lymphocytes, whereas type I expression was similar. The increased expression of type II mRNA in leukemic cells was closely linked with the increase in total IMPDH activity (r = 0.92). When leukemic cells from a patient with chronic granulocytic leukemia in blast crisis were separated into blast-rich and mature leukocyte-rich fractions, the expression of type II mRNA correlated positively with the population of immature leukemic cells, whereas type I expression was unchanged. Treatment of leukemic blasts with 12-O-tetradecanoyl-phorbol-13-acetate for 5 days resulted in a 90% decrease in the expression of type II mRNA with macrophage-like differentiation, while the expression of type I mRNA was relatively stable. These observations suggest that expression of type II IMPDH is stringently linked with immature characteristics of leukemic cells; thus, it should be a selective target for antileukemic chemotherapy.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0008-5472
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
51
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3886-90
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:1677309-Cell Differentiation,
pubmed-meshheading:1677309-DNA,
pubmed-meshheading:1677309-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:1677309-Gene Expression Regulation, Leukemic,
pubmed-meshheading:1677309-Hematopoietic System,
pubmed-meshheading:1677309-Humans,
pubmed-meshheading:1677309-IMP Dehydrogenase,
pubmed-meshheading:1677309-Isoenzymes,
pubmed-meshheading:1677309-Leukemia,
pubmed-meshheading:1677309-RNA, Messenger,
pubmed-meshheading:1677309-Up-Regulation
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pubmed:year |
1991
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pubmed:articleTitle |
Selective up-regulation of type II inosine 5'-monophosphate dehydrogenase messenger RNA expression in human leukemias.
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pubmed:affiliation |
Department of Medicine, Indiana University School of Medicine, Indianapolis 46202-5200.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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