Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Genome-wide methylation profiling of KMT2A-rearranged infant Acute Lymphoblastic Leukemia (ALL) cells after treatment with azacitidine, decitabine and zebularine

ABSTRACT: Genome-wide methylation profiling was performed on six cell lines derived from infants with KMT2A-rearranged ALL following treatment with three hypomethylating drugs (azacitidine, decitabine and zebularine) administered at low doses for 72 hours in vitro. We identified drug-specific and common differentially methylated regions and validated differentially expressed genes located within such regions, indicating commonalities in pathways targeted by azacitidine and decitabine in KMT2A-rearranged infant ALL. Of the three drugs, the most significant degree of hypomethylation was induced by decitabine followed by azacitidine, whereas zebularine did not exert a significant hypomethylating effect.

ORGANISM(S): Homo sapiens

PROVIDER: GSE198679 | GEO | 2022/12/31

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Transcriptomic profiling of KMT2A-rearranged infant acute lymphoblastic leukemia (ALL) cells after treatment witith azacitidine and decitabine.

Project description:Transcriptomic profiling was performed on six cell lines derived from infants with KMT2A-rearranged ALL following treatment with two hypomethylating drugs (azacitidine and decitabine) administered at low doses for 72 hours in vitro. We identified changes in gene expression following treatment with hypomethylating agents, with decitabine exerting a greater effect than azacitidine.

2022-12-31 | GSE212591 | GEO

Genome-wide methylation profiling of KMT2A-rearranged infant Acute Lymphoblastic Leukemia (ALL) cells after treatment with azacitidine, decitabine and zebularine

Project description:Genome-wide methylation profiling of KMT2A-rearranged infant Acute Lymphoblastic Leukemia (ALL) cells after treatment with azacitidine, decitabine and zebularine

| PRJNA816445 | ENA

Transcriptomic profiling of KMT2A-rearranged infant acute lymphoblastic leukemia (ALL) cells after treatment witith azacitidine and decitabine.

Project description:Transcriptomic profiling of KMT2A-rearranged infant acute lymphoblastic leukemia (ALL) cells after treatment witith azacitidine and decitabine.

| PRJNA876215 | ENA

Phosphoproteomics of primary acute myeloid leukemia cells with rearranged KMT2A

Project description:Acute myeloid leukemia (AML) is a disease with poor outcome but patients harbouring certain chromosomal rearrangements or complex karyotypes have particularly adverse prognosis. For these patients, targeted therapies have not yet made a significant clinical impact. To understand the molecular landscape of poor risk AML we profiled 55 poor risk AML patients using a multiomics approach that included transcriptomics (n=39), proteomics (n=55), phosphoproteomics (n=55) and an ex vivo drug sensitivity screening (482 compounds tested in at least 30 patients). We identified a phosphoproteomics signature that define two biologically distinct groups of KMT2A rearranged leukaemia, which we term MLLGA and MLLGB. MLLGA presented increased DOT1L phosphorylation, HOXA gene expression, CDK1 activity and phosphorylation of proteins involved in RNA metabolism, replication and DNA damage when compared to MLLGB and no KMT2A rearranged samples. MLLGA was particularly sensitive to 15 compounds including genotoxic drugs and inhibitors of mitotic kinases and IMPDH relative to other cases. The expression of IMPDH2 and multiple nucleolar proteins was higher in MLLGA and correlated with the response to IMPDH inhibition in KMT2A rearranged leukaemia, suggesting a role of the nucleolar activity in sensitivity to IMPDH inhibition. In summary, our multilayer molecular profiling of poor risk AML matched to the response to hundreds of compounds identified a phosphoproteomics signature that define two biologically and phenotypically distinct groups of KMT2A rearranged leukaemia. These data provide a rationale for the development of specific therapies for KMT2A subgroups characterised by the MLLGA phosphoproteomics signature identified in this study.

2023-03-11 | PXD036669 | Pride

Preclinical efficacy of azacitidine and venetoclax for infant KMT2A-rearranged ALL reveals a new therapeutic strategy

Project description:Preclinical efficacy of azacitidine and venetoclax for infant KMT2A-rearranged ALL reveals a new therapeutic strategy

| PRJNA876211 | ENA

Phosphoproteomics defines two biologically distinct groups of KMT2A rearranged acute myeloid leukaemia with different drug response phenotypes

2023-03-11 | PXD032980 | Pride

Proteasome Inhibition Targets the KMT2A Transcriptional Complex

Project description:We quantitatively evaluated H2Bub and H3K79me2 epigenetic marks genome wide in a KMT2A rearranged B lineage acute lymphoblastic leukemia cell line after treatment with bortezomib over a 6 hour time course by ChIP-Rx. We identified rapid and concordant depletion of these epigenetic marks within two hours. To look at gene expression changes, RNA sequencing was performed on KMT2A rearranged B lineage acute lymphoblastic leukemia patient samples in the presence and absence of bortezomib exposure.

2022-01-13 | GSE152816 | GEO

KMT2A oncoproteins induce epigenetic resistance to targeted therapies.

Project description:Chromosomal translocations involving the Lysine-Methyl-Tansferase-2A (KMT2A) locus generate potent oncogenes that cause highly aggressive acute leukemias KMT2A and the most frequent translocation partners encode proteins that interact with DNA to regulate developmental gene expression. KMT2A-oncogenic fusion proteins (oncoproteins) contribute to the epigenetic mechanisms that allow KMT2A-rearranged leukemias to evade targeted therapies. By profiling the oncoprotein-target sites of 34 KMT2A-rearranged leukemia samples, we find that the genomic enrichment of oncoprotein binding is highly variable between samples. At high levels of expression, the oncoproteins preferentially activate either the lymphoid or myeloid lineage program depending on the fusion partner. These fusion-partner-dependent binding sites correspond to the frequencies of each mutation in acute lymphoid leukemia versus acute myeloid leukemia. By profiling a sample that underwent a lymphoid-to-myeloid lineage switching event in response to lymphoid-directed treatment, we find the global oncoprotein levels are reduced and the oncoprotein-target gene network changes. At lower levels of expression, the oncoprotein shifts to a non-canonical regulatory program that favors the myeloid lineage, and in a subset of resistant patients, the Menin inhibitor Revumenib induces a similar response. The dynamic shifts in KMT2A oncoproteins we describe likely contribute to epigenetic resistance of KMT2A-rearranged leukemias to targeted therapies.

2024-09-27 | GSE252378 | GEO

RNA-seq analysis of human KMT2A rearranged Molm14 AML cell line treated with DOT1L and/or EZH2 inhibitor

Project description:The histone methyltransferases DOT1L (H3K79me1,2,3 KMT, "activating" chromatin mark) and EZH2 (H3K27me1,2,3 KMT, "silencing" mark) have both been shown to be required for growth and survival of KMT2A rearranged AML cells. Both KMTs have been shown to modulate expression of HOXA cluster genes, albeit for EZH2 this has not been shown in the context of KMT2A rearranged AML, but in other subtypes of AML. We asked what transcriptional effects dual inhibition of DOT1L and EZH2 has in KMT2A rearranged AML.

2020-04-29 | GSE149520 | GEO

RNA-seq analysis of human KMT2A rearranged MV4;11 AML cell line treated with DOT1L and/or EZH2 inhibitor

2019-07-17 | GSE134369 | GEO