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- W2891694193 abstract "Background: Myeloproliferative neoplasms (MPNs) are clonal hematological malignancies with an inherent tendency to progress to acute leukemia, after a variable period of time. Although the mechanisms involved in the disease transformation are still unclear, it´s known that transcription factor RUNX1 (AML1) is frequently deregulated in human leukemia, and recently, it has been described that the activity of RUNX1 together with CBF-β cofactor is regulated by the proteins p300 and HIPK2. In fact, HIPK2 phosphorylates both RUNX1 and p300, activating the whole transcriptional complex. Therefore, the study of the status of this complex seems to be interesting in order to understand the mechanisms involved in the leukemic transformation. Methods: Our aim is to study the effect of different typical drugs in several NMPs cell lines and patient samples with differential expression of these genes and compare it with a context where the complex is downregulated. For this purpose, we knocked down some genes of the studied complex before the treatment and then performed different viability, apoptosis and cell cycle assays, to elucidate if the status of these genes could play an important role in the response to the different biochemical drugs tested, showing a new approach to these diseases and giving us new strategies to study the molecular changes that occur during leukemic transformation. Results: Here we show that the state of the Runx1/CBF-BETA/P300/Hipk2 can play a critical role for the progression of the Chronic Myeloproliferative Neoplasms. Conclusions: The functional status of the components of the complex and its deregulation, could be playing an important role in the progression of leukemogenesis in the Chronic Myeloproliferative Neoplasms. Legal entity responsible for the study: Instituto de Salud Carlos III. Ministery of Sciences. Govern of Spain. Funding: Instituto de Salud Carlos III. Disclosure: All authors have declared no conflicts of interest." @default.
- W2891694193 created "2018-09-27" @default.
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- W2891694193 date "2018-09-01" @default.
- W2891694193 modified "2023-09-26" @default.
- W2891694193 title "Study of toxicity of the conventional treatments in myeloproliferative neoplasms, based on the functional status of the RUNX1/CBF-BETA/P300/HIPK2 complex" @default.
- W2891694193 doi "https://doi.org/10.1093/annonc/mdy314.042" @default.
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