Novel epigenetic based differentiation therapy for Acute Myeloid Leukemia
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ABSTRACT: We have identified and characterized two lysine (K) deacetylase inhibitors (DACi), CM-444 and CM-1758. These inhibitors demonstrate the ability to promote myeloid differentiation in all acute myeloid leukemia (AML) subtypes at low, non-cytotoxic doses, setting them apart from other commercially available histone deacetylase inhibitors (HDACi). Upon analysis of the acetylome following treatment with CM-444 and CM-1758, we observed modulation of non-histone proteins involved in the enhancer–promoter chromatin regulatory complex, including bromodomain proteins (BRDs). This acetylation is crucial for enhancing the expression of key transcription factors directly involved in the differentiation therapy induced by CM-444 and CM-1758 in AML. In summary, these compounds present promising potential as effective differentiation-based therapeutic agents across AML subtypes, offering a novel mechanism for the treatment of AML
INSTRUMENT(S): Orbitrap Exploris 480
ORGANISM(S): Homo Sapiens (human)
TISSUE(S): Cell Culture
DISEASE(S): Acute Leukemia
SUBMITTER: Fernando Garcia
LAB HEAD: Fernando Garcia Martinez
PROVIDER: PXD050623 | Pride | 2024-06-03
REPOSITORIES: Pride
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