AI Article Synopsis
- Chromosomal translocation 8;21 is common in acute myeloid leukemia (AML) and leads to the fusion protein AML1-ETO (AE), which promotes leukemia development.
- The alternative splicing of AE, specifically the isoform AE9a, exhibits full transforming capabilities in human and murine models but requires higher expression levels for full activity.
- When AE and AE9a are cointroduced, AE-expressing cells are favored, with AE9a showing less selection pressure, and AE9a demonstrates impaired regulation of target genes unless expressed at high levels.
Article Abstract
Chromosomal translocation 8;21 is found in 40% of the FAB M2 subtype of acute myeloid leukemia (AML). The resultant in-frame fusion protein AML1-ETO (AE) acts as an initiating oncogene for leukemia development. AE immortalizes human CD34(+) cord blood cells in long-term culture. We assessed the transforming properties of the alternatively spliced AE isoform AE9a (or alternative splicing at exon 9), which is fully transforming in a murine retroviral model, in human cord blood cells. Full activity was realized only upon increased fusion protein expression. This effect was recapitulated in the AE9a murine AML model. Cotransduction of AE and AE9a resulted in a strong selective pressure for AE-expressing cells. In the context of AE, AE9a did not show selection for increased expression, affirming observations of human t(8;21) patient samples where full-length AE is the dominant protein detected. Mechanistically, AE9a showed defective transcriptional regulation of AE target genes that was partially corrected at high expression. Together, these results bring an additional perspective to our understanding of AE function and highlight the contribution of oncogene expression level in t(8;21) experimental models.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4987773 | PMC |
| http://dx.doi.org/10.1073/pnas.1524225113 | DOI Listing |
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Article Synopsis
- Chromosomal translocation 8;21 is common in acute myeloid leukemia (AML) and leads to the fusion protein AML1-ETO (AE), which promotes leukemia development.
- The alternative splicing of AE, specifically the isoform AE9a, exhibits full transforming capabilities in human and murine models but requires higher expression levels for full activity.
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[Monitoring the expression ratio of AML1-ETO9a isoform in t(8;21) acute myeloid leukemia and its significance].
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Objective: To study the expression ratio of AML1-ETO9a (AE9a) isoform in t(8;21) acute myeloid leukemia (AML) and its clinical significance.
Methods: Bone marrow samples from 44 newly diagnosed t(8;21) AML patients co-expressed AE9a and AE were screened by RT-PCR. The alteration of the AE9a expression ratio was monitored during follow-up by using quantitative real-time RT-PCR (qPCR).
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