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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2002-10-14
pubmed:abstractText
When NF-kappaB proteins are bound to IkappaBalpha, they remain in the cytosol, and are unable to act as transcription factors. Phosphorylation of IkappaBalpha at Serine32 and Serine36 has been shown to stimulate ubiquitination followed by proteasome-mediated degradation of IkappaBalpha, resulting in the release of active NF-kappaB. NF-kappaB activity is associated with bone loss and B cell growth as well as chemotherapy resistance. Because previous studies have shown abnormalities of the IkappaBalpha gene in patients with lymphoma, we determined whether alterations of this gene also occur in multiple myeloma (MM). We determined the DNA sequence of the IkappaBalpha gene from bone marrow mononuclear cells from 18 MM patients and 24 healthy subjects as well as two MM cell-lines. We identified eight polymorphisms. Statistically, the prevalence of three polymorphisms, one in exon 1 and two in exon 6, were significantly higher in MM patients (alpha>1) compared with samples from control subjects. Six of eight polymorphisms in myeloma samples have also been identified in previous studies of IkappaBalpha sequences derived from lymphoma samples. In addition, we detected two polymorphisms in the IkappaBalpha gene that have not been previously reported. Together, these results provide the basis for future evaluation the IkappaBalpha/NF-kappaB pathway in MM patients.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0165-4608
pubmed:author
pubmed:issnType
Print
pubmed:volume
137
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
43-8
pubmed:dateRevised
2005-11-17
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Identification of polymorphisms of the IkappaBalpha gene associated with an increased risk of multiple myeloma.
pubmed:affiliation
Division of Hematology and Oncology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
pubmed:publicationType
Journal Article