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Nucleoporin 98 related leukemia: Role of retinoblastoma protein and discovery of proteins associated with HOXA9 in NUP98-HOXA9 environment

par Barros Vaz, Marcela
Président du jury Droogmans, Louis
Promoteur Vanhamme, Luc
Publication Non publié, 2021-12-13

Thèse de doctorat

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Résumé :

Chromosomal translocations that involve the nucleoporin NUP98 are recurrent in childhood therapy-related acute myeloid leukemias, characterized by disruption of normal hematopoiesis and bone marrow failure. Previous experiments showed that the expression of Nup98 fusion proteins leads to changes in nuclear envelope architecture and HOXA9 overexpression. My work provided new data supporting a mechanical function of RB in the nuclear architecture of NUP98 fusions, disclosing a possible mechanism of action involving the chromatin regulators. Furthermore, new pieces of evidence on HOXA9 regulation mediated by NUP98-related leukemia were revealed, which might be interesting for new target identification for the treatment of HOXA9-overexpressing diseases