Linked Life Data

15585651

Source:http://linkedlifedata.com/resource/pubmed/id/15585651

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2005-3-22
pubmed:abstractText
FMS-like tyrosine kinase 3 (FLT3) is a receptor tyrosine kinase that is constitutively activated in approximately 30% of acute myelogenous leukemia (AML) patients and appears to confer an adverse prognosis. Thus, development of inhibitors and/or antibodies that specifically target FLT3 has been of substantial interest. In this regard, phase 1 and 2 trials involving FLT3 inhibitors have recently reported FLT3 inhibition and leukemic blast reduction in some patients. Despite this, issues such as specificity and resistance need to be addressed. Consequently, the development of alternative approaches for targeting FLT3 would be of great consequence. In the present report, we demonstrate that FLT3 siRNA effectively down-regulates FLT3 expression in Ba/F3 cells transfected with FLT3 containing an activating internal tandem duplication (ITD) in the juxtamembrane domain and FLT3-ITD-positive Molm-14 human leukemia cells. Treatment with the FLT3 siRNA results in growth inhibition and apoptosis of these cells. Furthermore, siRNA-induced down-regulation of FLT3 increased the sensitivity of both cell lines to treatment with the FLT3 inhibitor MLN518. This illustrates the potential benefit of combined therapeutic approaches.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
105
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2952-4
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
RNAi-induced down-regulation of FLT3 expression in AML cell lines increases sensitivity to MLN518.
pubmed:affiliation
Department of Hematology and Oncology, Howard Hughes Medical Institute, Oregon Health and Science University, and Portland Veterans Affairs (VA) Medical Center, 3181 Sam Jackson Park Rd, Portland, OR 97239, USA. waltersd@ohsu.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't