The RUNX1/RUNX1T1 network: translating insights into therapeutic options

RUNX1/RUNX1T1 is the most common fusion gene found in acute myeloid leukemia. Seminal contributions by many different research groups have revealed a complex regulatory network promoting leukemic self-renewal and propagation. Perturbation of RUNX1/RUNX1T1 levels and its DNA binding affects chromatin...

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Detalles Bibliográficos
Autores principales: Swart, Laura E., Heidenreich, Olaf
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Science Inc 2021
Materias:
Review Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7854360/
https://www.ncbi.nlm.nih.gov/pubmed/33217477
http://dx.doi.org/10.1016/j.exphem.2020.11.005
Descripción
Sumario:RUNX1/RUNX1T1 is the most common fusion gene found in acute myeloid leukemia. Seminal contributions by many different research groups have revealed a complex regulatory network promoting leukemic self-renewal and propagation. Perturbation of RUNX1/RUNX1T1 levels and its DNA binding affects chromatin accessibility and transcription factor occupation at multiple gene loci associated with changes in gene expression levels. Exploration of this transcriptional program by targeted RNAi screens uncovered a crucial role of RUNX1/RUNX1T1 in cell cycle progression by regulating CCND2. This dependency results in a high vulnerability toward inhibitors of CDK4 and CDK6 and suggests new avenues for therapeutic intervention against acute myeloid leukemia.

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