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AML1/MTG8 oncogene suppression by small interfering RNAs supports myeloid differentiation of t(8;21)-positive leukemic cells.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Heidenreich, O. Krauter, Jürgen G. E. Riehle, Heidemarie Hadwiger, Philipp John, Matthias Heil, Gerhard Vornlocher, Hans-Peter |
| Copyright Year | 2003 |
| Abstract | The translocation t(8;21) yields the leukemic fusion gene AML1/MTG8 and is associated with 10%-15% of all de novo cases of acute myeloid leukemia. We demonstrate the efficient and specific suppression of AML1/MTG8 by small interfering RNAs (siRNAs) in the human leukemic cell lines Kasumi-1 and SKNO-1. siRNAs targeted against the fusion site of the AML1/MTG8 mRNA reduce the levels of AML1/MTG8 without affecting the amount of wild-type AML1. These data argue against a transitive RNA interference mechanism potentially induced by siRNAs in such leukemic cells. Depletion of AML1/MTG8 correlates with an increased susceptibility of both Kasumi-1 and SKNO-1 cells to tumor growth factor beta(1) (TGF beta(1))/vitamin D(3)-induced differentiation, leading to increased expression of CD11b, macrophage colony-stimulating factor (M-CSF) receptor, and C/EBP alpha (CAAT/enhancer binding protein). Moreover, siRNA-mediated AML1/MTG8 suppression results in changes in cell shape and, in combination with TGF beta(1)/vitamin D(3), severely reduces clonogenicity of Kasumi-1 cells. These results suggest an important role for AML1/MTG8 in preventing differentiation, thereby propagating leukemic blast cells. Therefore, siRNAs are promising tools for a functional analysis of AML1/MTG8 and may be used in a molecularly defined therapeutic approach for t(8;21)-positive leukemia. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.bloodjournal.org/content/bloodjournal/101/8/3157.full.pdf?sso-checked=true |
| PubMed reference number | 12480707v1 |
| Volume Number | 101 |
| Issue Number | 8 |
| Journal | Blood |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Cell Differentiation process Chronic Lymphocytic Leukemia Colony-Stimulating Factors Cultured Cell Line Enhancer of transcription Leukemia, B-Cell Leukemia, Myelocytic, Acute Leukemic Cell Myeloid Cell Differentiation Neoplasms Oncogenes RUNX1/RUNX1T1 Fusion Gene Stimulation (motivation) acute myeloid leukemia 1 protein negative regulation of transforming growth factor beta activation t(8;21) |
| Content Type | Text |
| Resource Type | Article |
