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Inhibition of bcr-abl gene expression by small interfering RNA sensitizes for imatinib mesylate (STI571).
| Content Provider | Semantic Scholar |
|---|---|
| Author | Wohlbold, Lara Kuip, Heiko Van Der Miething, Cornelius Vornlocher, Hans-Peter Knabbe, Cornelius Duyster, Justus Aulitzky, Walter Erich |
| Copyright Year | 2003 |
| Abstract | Bcr-Abl proteins are effective inducers of the leukemic phenotype in chronic myeloid leukemia (CML) and distinct variants of acute lymphoblastic leukemia (ALL). Targeting bcr-abl by treatment with the selective tyrosine kinase inhibitor imatinib has proved to be highly efficient for controlling leukemic growth. However, it is unclear whether imatinib is sufficient to eradicate the disease because of primary or secondary resistance of leukemic cells. Therefore, targeting Bcr-Abl with an alternative approach is of great interest. We demonstrate that RNA interference (RNAi) with a breakpoint-specific short-interfering RNA (siRNA) is capable of decreasing Bcr-Abl protein expression and of antagonizing Bcr-Abl-induced biochemical activities. RNAi selectively inhibited Bcr-Abl-dependent cell growth. Furthermore, bcr-abl-homologous siRNA increased sensitivity to imatinib in Bcr-Abl-overexpressing cells and in a cell line expressing the imatinib-resistant Bcr-Abl kinase domain mutation His396Pro, thereby antagonizing 2 of the major mechanisms of resistance to imatinib. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://bloodjournal.hematologylibrary.org/content/early/2003/05/15/blood-2002-12-3899.full.pdf |
| Alternate Webpage(s) | http://bloodjournal.hematologylibrary.org/content/102/6/2236.full.pdf |
| PubMed reference number | 12750174v1 |
| Volume Number | 102 |
| Issue Number | 6 |
| Journal | Blood |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | B-Cell Receptor Complex Biospecimen Core Resource Facility Gene Expression Imatinib mesylate Mutation Myeloid Leukemia Myeloid Leukemia, Chronic Non-Small Cell Lung Carcinoma Precursor Cell Lymphoblastic Leukemia Lymphoma Protein Tyrosine Kinase Protein-tyrosine kinase inhibitor RNA Interference protein expression |
| Content Type | Text |
| Resource Type | Article |