Linked Life Data

8683999

Source:http://linkedlifedata.com/resource/pubmed/id/8683999

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
1996-8-20
pubmed:abstractText
We have developed a method to quantify topoisomerase (topo) II activities in partially purified nuclear extracts from human leukemia cells. By virtue of their different pH optima in the reaction buffer, two different topo II activities were found with activity optima at pH 7.9 and at pH 8.9 under high stringency conditions. The activities could be identified as topo II beta activity (pH 7.9) and topo II alpha activity (pH 8.9) by their different sensitivities to topo II alpha inhibitors, dephosphorylation experiments and immunoprecipitation with polyclonal antibodies. Seventy-two bone marrow or blood samples from patients with acute myeloid leukemias have been examined and their in vitro sensitivities to anthracyclines and epipodophyllotoxines correlated to the activities of topo II alpha and topo II beta. Although the topo II alpha activity could be directly inhibited by incubation of the cells with the mentioned drugs, no correlation between the topo II alpha activity and the sensitivity of the cells could be found. In contrast, the topo II beta activity which was not substantially inhibited by the drugs inversely correlated with the sensitivity of the cells. These findings were statistically significant for idarubicin (P= 0.017) and daunorubicin (P = 0.006). Vice versa, resistant cells (IC50 > median) had a higher topo II beta activity. Clinical relevance might be indicated by the finding that cells from patients that relapsed after initial treatment with anthracyclin-containing regiments had a significantly higher topo II alpha/beta activity ratio (P=0.0276). Obviously, the sensitivity of AML cells is substantially influenced by the activity of the resistant topo II (topo II beta) which gives evidence that the remaining topo II activity after treatment helps the cell to survive the DNA repair phase.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0887-6924
pubmed:author
pubmed:issnType
Print
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1177-80
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Topoisomerase II activities in AML and their correlation with cellular sensitivity to anthracyclines and epipodophyllotoxines.
pubmed:affiliation
Medizinische Poliklinik, Medical School, University of Wuerzberg, Germany.
pubmed:publicationType
Journal Article