Conséquences et mécanismes des activités génétiques et épigénétiques du facteur de transcription SPI1 dans la leucémogenèse

par Lélia Polit

Projet de thèse en Sciences de la vie et de la santé

Sous la direction de Valentina Boeva et de Christel Guillouf.

Thèses en préparation à Paris Saclay , dans le cadre de École doctorale Structure et Dynamique des Systèmes Vivants (Gif-sur-Yvette, Essonne) , en partenariat avec Institut Cochin (laboratoire) et de Université Paris-Sud (établissement de préparation de la thèse) depuis le 30-09-2017 .


  • Résumé

    Hematopoiesis is a finely regulated program that controls the production of blood cells. Acute Myeloid Leukemias (AMLs) are due to the progressive accumulation of mutations in myeloid progenitors. Those mutations alter proteins of signalling networks controlling proliferation and growth factor dependency and proteins that affect transcription factors (TFs) controlling cell fate decisions. It has been shown that the precise control of TF activity is essential for normal hematopoietic differentiation. Indeed, genetic alterations of a hematopoietic TF participate to the lineage specificity of the AML by their action in blocking differentiation into a specific lineage. Recent studies suggest that epigenetic regulators such as TET2/DNMT3a pathway on DNA methylation and PcG complexes also control normal hematopoiesis and contribute to leukemogenesis. TFs and epigenetic regulators control gene expression, RNA splicing and other processes related to DNA, such as replication and repair. However, we are far from understanding how TFs and epigenetic regulation control these mechanisms and, more specifically, how they are interconnected. Our work participates to the general objective of understanding how TFs act on genetic and epigenetic mechanisms in leukemias. The project will focus on understanding specific roles of the TF Spi1/PU.1 in leukemic development. Spi1/PU.1 binds to DNA and RNA and interacts with several proteins involved in epigenetic regulation, alternative splicing and transcriptional co-factors. The final goal is to draw a global view of the role of Spi1 in controlling DNA and RNA metabolism and how the alteration of these processes may be involved in leukemogenesis.

  • Titre traduit

    Consequences and mecanismes of genetic and epigenetic activities of Spi1 transcription factor in leukemogenesis


  • Résumé

    Hematopoiesis is a finely regulated program that controls the production of blood cells. Acute Myeloid Leukemias (AMLs) are due to the progressive accumulation of mutations in myeloid progenitors. Those mutations alter proteins of signalling networks controlling proliferation and growth factor dependency and proteins that affect transcription factors (TFs) controlling cell fate decisions. It has been shown that the precise control of TF activity is essential for normal hematopoietic differentiation. Indeed, genetic alterations of a hematopoietic TF participate to the lineage specificity of the AML by their action in blocking differentiation into a specific lineage. Recent studies suggest that epigenetic regulators such as TET2/DNMT3a pathway on DNA methylation and PcG complexes also control normal hematopoiesis and contribute to leukemogenesis. TFs and epigenetic regulators control gene expression, RNA splicing and other processes related to DNA, such as replication and repair. However, we are far from understanding how TFs and epigenetic regulation control these mechanisms and, more specifically, how they are interconnected. Our work participates to the general objective of understanding how TFs act on genetic and epigenetic mechanisms in leukemias. The project will focus on understanding specific roles of the TF Spi1/PU.1 in leukemic development. Spi1/PU.1 binds to DNA and RNA and interacts with several proteins involved in epigenetic regulation, alternative splicing and transcriptional co-factors. The final goal is to draw a global view of the role of Spi1 in controlling DNA and RNA metabolism and how the alteration of these processes may be involved in leukemogenesis.