Defining the role of HIF-2alpha in the pathogenesis of acute myeloid leukemia and exploiting its inhibition as a new therapeutic approach to promote leukemia differentiation and exhaustion
Description
This dataset represents findings obtained within a project supported by the Italian Ministry of Health (project code: RF-2019-12369841) and focused on investigating the mechanism of myeloid differentiation blockade by the transcription factor HIF-2alpha in acute myeloid leukemia (AML) and the consequences of its inhibition with novel targeted therapies. We found that in AML HIF-2alpha regulates a specific set of target genes involved in transcriptional repression, leading to inhibition of entire gene clusters linked to myeloid difefrentiation. As a consequence, HIF-2alpha blockade via genetic or pharmacologic approaches leads to myeloid differentiation and leukemia debulking. Also, we positioned HIF-2alpha under direct transcriptional control by the prodifferentiation agent all-trans retinoic acid (ATRA) and demonstrated that HIF-2alpha blockade cooperates with ATRA to trigger AML cell differentiation. Links related to this dataset contain: 1. A publication describing part of the results funded by this grant; 2. Source data linked to this publication and deposited in the BioStudies repository (accession number: S-SCDT-10_15252-EMMM_202317810); 3. Sequencing data deposited in the GEO repository.
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Funding
Ministero della Salute
RF-2019-12369841