T cell receptor repertoire in AML
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB48020 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR8980120_1.fastq.gz | Fastqsanger.gz | |||
| ERR8980120_2.fastq.gz | Fastqsanger.gz | |||
| ERR8980150_1.fastq.gz | Fastqsanger.gz | |||
| ERR8980150_2.fastq.gz | Fastqsanger.gz | |||
| ERR8980160_1.fastq.gz | Fastqsanger.gz |
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Project description:An increasing body of work reveals aberrant hypermethylation of genes occurring in and potentially contributing to the pathogenesis of myeloid malignancies. Several of these diseases, such as myelodysplastic syndromes (MDS), are responsive to DNA methyltransferase inhibitors. In order to determine the extent of promoter hypermethylation in such tumors we compared the distribution of DNA methylation of 14,000 promoters in MDS and secondary AML patients enrolled in a phase I trial of 5-azacytidine and the histone deacetylase inhibitor entinostat against de novo AML patients and normal CD34+ bone marrow cells. The MDS and secondary AML patients displayed more extensive aberrant DNA methylation involving thousands of genes than did the normal CD34+ bone marrow cells or de novo AML blasts. Aberrant methylation in MDS and secondary AML tended to affect particular chromosomal regions, occurred more frequently in Alu poor genes, and included prominent involvement of genes involved in the WNT and MAPK signaling pathways. DNA methylation was also measured at days 15 and 29 after the first treatment cycle. DNA methylation was reversed at day 15 in a uniform manner throughout the genome, and this effect persisted through day 29, even without continuous administration of the study drugs. Keywords: DNA methylation profiling
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Project description:The whole exome sequencing experiment is part of the study: “Analysis of 5-azacytidine resistance models reveals a set of targetable pathways”. In the study we generated myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) OCI-M2 cell lines as well as patient-derived bone marrow cell lines that are resistant to hypomethylating therapy by 5-azacytidine (AZA). By integrated analysis of expression and mutation data obtained from these samples we have identified multiple signaling pathways whose modulation by specific small molecule inhibitors significantly block proliferation of AZA-resistant cell lines without increasing their sensitivity to AZA. The understanding of the molecular mechanisms which characterize the AZA-R phenotype can be used for broadening therapeutic options at progressing states during AZA therapy.
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