Project description:Transcriptional deregulation plays a major role in acute myeloid leukemia, identification of epigenetic modifying enzymes essential for the maintenance of oncogenic transcription programs holds the key to better understanding the biology and designing effective therapeutic strategies for the disease. Here we provide experimental evidence showing the functional involvement and therapeutic potentials of targeting PRMT1 with H4R3 methyltransferase activity in various MLL and non-MLL leukemias. PRMT1 is necessary but not sufficient for leukemic transformation, which requires co-recruitment of KDM4C with H3K9 demethylase activity by chimeric transcription factors to mediate epigenetic reprogramming. Inhibition of KDM4C/PRMT1 suppresses transcription and transformation ability of MLL fusions and MOZ-TIF2, revealing a novel and targetable epigenetic circuitry mediated by PRMT1 and KDM4C in acute leukemia.
Project description:We report the DNA methylation and transcriptional molecular features of paired diagnosis and relapsed Acute Myeloid Leukemia samples
Project description: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
Project description:Label-free quantitation dataset from 44 representative Acute Myeloid Leukemia (AML) patients from the LAML TCGA dataset, and 6 healthy bone marrow derived controls including 3 lineage-depleted and 3 CD34+ selected bone marrows.
Project description:A deep-scale proteome and phosphoproteome database from 44 representative Acute Myeloid Leukemia (AML) patients from the LAML TCGA dataset, and 6 healthy bone marrow derived controls including 3 lineage-depleted and 3 CD34+ selected bone marrows.