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National Repository of Grey Literature 1 records found  Search took 0.00 seconds. 
Kolokalizace PML tělísek a PML/RARa mikroohnisek s utlumenými a aktivovanými genetickými lokusy a změny struktury chromatinu u APL leukemických buněk
 Falk, Martin ; Lukášová, Emilie ; Faretta, M. ; Dellino, I. ; Kozubek, Stanislav ; Pellici, G. I. ; Kozubek, Michal ; Rochi, M.
Acute promyelocytic leukemia (APL) is associated with the reciprocal translocation between PML and RARa genes; however, the mechanism of its pathogenesis is still not well understood. In this article we demonstrate that PML/RARa fusion protein colocalizes with particular chromosomal loci containing clusters of genes downregulated by this protein. Binding of PML/RARa to those loci is consequently followed by local chromatin contraction. Treatment of leukemic cells with retinoic acid (ATRA) leads to reconstruction of PML bodies and reverts chromatin condensation to original value in healthy cells. Therefore we propose and discuss the mechanistic model of downregulation in APL based on the strong attraction of histone deacethylases (HDAC) to downregulated loci by the PML/RARa fusion chimera.
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