Temporal resolution by multiomic approaches of acute myeloid leukemias
Acute myeloid leukemias (AMLs) are a type of cancer where undifferentiated myeloid cells abnormally proliferate. Such phenotype can be caused by the expression of chimeric proteins like PML-RARα and MLL-AF9. Many studies analyze the final stage of the disease, without focusing on its initiation and...
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| Formato: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2024 |
| País: | España |
| Recursos: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/690384 |
| Acesso em linha: | http://hdl.handle.net/10803/690384 |
| Access Level: | acceso embargado |
| Palavra-chave: | Leukemia Epigenetic Phf19 Leucemia Epigenetica 575 |
| Resumo: | Acute myeloid leukemias (AMLs) are a type of cancer where undifferentiated myeloid cells abnormally proliferate. Such phenotype can be caused by the expression of chimeric proteins like PML-RARα and MLL-AF9. Many studies analyze the final stage of the disease, without focusing on its initiation and development, which start from healthy blood cells. Hence, we generated in vitro leukemic models that enabled us to measure the temporal transcriptomic changes orchestrated by PML-RARα and to evaluate the impact of an altered epigenetic landscape on MLL-AF9 leukemogenesis. Firstly, we studied the importance of Klf4 downregulation for the PML-RARα immortalization process. Secondly, we studied the role of a Polycomb-associated protein, called Phf19, whose depletion in healthy hematopoietic cells, prior expression of MLL-AF9, enhanced the acquisition of more aggressive traits. These data were thoroughly compared with AML patient’s datasets, which confirmed the molecular and functional results generated with these models. This study reveals how specific transcriptomics and epigenomic programs are intimately linked with AML prognosis. |
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