Novel epigenetic based differentiation therapy for Acute Myeloid Leukemia
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1114031 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29098259_1.fastq.gz | Fastqsanger.gz | |||
| SRR29098259_2.fastq.gz | Fastqsanger.gz | |||
| SRR29098260_1.fastq.gz | Fastqsanger.gz | |||
| SRR29098260_2.fastq.gz | Fastqsanger.gz | |||
| SRR29098261_1.fastq.gz | Fastqsanger.gz |
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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
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Project description:Novel epigenetic based differentiation therapy for Acute Myeloid Leukemia
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Project description:Despite the development of novel therapies for acute myeloid leukemia (AML), outcomes remain poor for most patients, and therapeutic improvements are an urgent unmet need. Although treatment regimens promoting differentiation have succeeded in the treatment of acute promyelocytic leukemia (APL), their role in other AML subtypes needs to be explored. Here we identified and characterized two lysine (K) deacetylase inhibitors (DACi), CM-444 and CM-1758, exhibiting higher capacity to promote myeloid differentiation in all AML subtypes at low non-cytotoxic doses than commercial HDACi. Analyzing the acetylome after CM-444 and CM-1758 treatment revealed modulation of non-histone proteins involved in the enhancer–promoter chromatin regulatory complex, including bromodomain proteins (BRDs). This acetylation was essential for enhancing the expression of key transcription factors directly involved in the differentiation therapy provided by CM-444/CM-1758 in AML. In summary, these compounds may represent effective differentiation-based therapeutic agents across AML subtypes with a novel mechanism for treatment of AML.
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Project description:Despite the development of novel therapies for acute myeloid leukemia (AML), outcomes remain poor for most patients, and therapeutic improvements are an urgent unmet need. Although treatment regimens promoting differentiation have succeeded in the treatment of acute promyelocytic leukemia (APL), their role in other AML subtypes needs to be explored. Here we identified and characterized two lysine (K) deacetylase inhibitors (DACi), CM-444 and CM-1758, exhibiting capacity to promote myeloid differentiation in all AML subtypes at low non-cytotoxic doses unlike other commercial HDACi. Analyzing the acetylome after CM-444 and CM-1758 treatment revealed modulation of non-histone proteins involved in the enhancer–promoter chromatin regulatory complex, including bromodomain proteins (BRDs). This acetylation was essential for enhancing the expression of key transcription factors directly involved in the differentiation therapy induced by CM-444/CM-1758 in AML. In summary, these compounds may represent effective differentiation-based therapeutic agents across AML subtypes with a novel mechanism for treatment of AML.
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Project description:Antibody-based therapy for cancer is now one of the most successful and important strategies for treating patients with hematological malignancies. However, the lack of efficient tumor-associated antigens restricts the targeting therapy of myeloid leukemia. Analysis of the gene expression proï¬les of primary bone marrow samples from human acute myeloid leukemia (AML) patients or healthy donors was to identify and expand novel targets for the treatment of myeloid leukemias. we found that epithelial cell adhesion molecule (EpCAM) is overexpressed in patients with AML. we analyzed the gene expression proï¬les of bone marrow mononuclear cells from 2 human acute myeloid leukemia (AML) patients and 2 healthy donors using an oligonucleotide microarray, to identify up-regulated genes in AML samples comparing with healthy tissues.
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Project description:Despite the development of novel therapies for acute myeloid leukemia, outcomes remain poor for most patients, and therapeutic improvements are an urgent unmet need. Although treatment regimens promoting differentiation have succeeded in the treatment of acute promyelocytic leukemia, their role in other acute myeloid leukemia subtypes needs to be explored. Here we identify and characterize two lysine deacetylase inhibitors, CM-444 and CM-1758, exhibiting the capacity to promote myeloid differentiation in all acute myeloid leukemia subtypes at low non-cytotoxic doses, unlike other commercial histone deacetylase inhibitors. Analyzing the acetylome after CM-444 and CM-1758 treatment reveals modulation of non-histone proteins involved in the enhancer-promoter chromatin regulatory complex, including bromodomain proteins. This acetylation is essential for enhancing the expression of key transcription factors directly involved in the differentiation therapy induced by CM-444/CM-1758 in acute myeloid leukemia. In summary, these compounds may represent effective differentiation-based therapeutic agents across acute myeloid leukemia subtypes with a potential mechanism for the treatment of acute myeloid leukemia.
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