Linked Life Data

12538346

Source:http://linkedlifedata.com/resource/pubmed/id/12538346

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2003-1-22
pubmed:abstractText
Defects in the DNA mismatch repair (MMR) pathway have recently been shown to be associated with resistance to several of the cytotoxic drugs used in the treatment of children with acute lymphoblastic leukaemia (ALL). We have assessed the MMR status of a range of leukaemic cell lines using an in vitro repair assay and correlated this with protein expression of the best characterized components of the system. We have also assessed MMR in leukaemic blasts from a limited panel of children with ALL and related this to Ki67 expression as a measure of proliferative capacity. Out of nine leukaemic cell lines tested, five of the seven lymphoid lines showed little or no repair using the in vitro assay and had low MMR protein expression. In three (NALM-6, Reh and MOLT 4) MMR defects have not been previously reported. Immunohistochemistry of clinical samples showed a wide range of expression of MLH1, MSH2 and Ki67 in nine cases studied at presentation, with a highly statistically significant correlation between MLH1 and Ki67 expression (r(2) = 0.96, P < 0.0001, Pearson correlation). Western blotting demonstrated high expression of MLH1, PMS2, MSH2 and MSH6 proteins. In vitro analysis of G.T repair using lymphoblast cytosol from the same patients showed a wide range of proficiency, which was markedly reduced in one case studied at relapse. These results suggest that MMR defects are more common in leukaemic cell lines and acute lymphoblastic leukaemias than previously thought.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0143-3334
pubmed:author
pubmed:issnType
Print
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
31-8
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Assessment of mismatch repair function in leukaemic cell lines and blasts from children with acute lymphoblastic leukaemia.
pubmed:affiliation
The LRF Molecular Pharmacology Specialist Programme, Cancer Research Unit, Newcastle upon Tyne, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't