Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Genomic and epigenomic predictors of response to Guadecitabine in relapsed/refractory Acute Myelogenous Leukemia

ABSTRACT: Genomic and epigenomic predictors of response to Guadecitabine in relapsed/refractory Acute Myelogenous Leukemia

PROVIDER: PRJNA449238 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR6963600_1.fastq.gz	Fastqsanger.gz
	SRR6963600_2.fastq.gz	Fastqsanger.gz
	SRR6963610_1.fastq.gz	Fastqsanger.gz
	SRR6963610_2.fastq.gz	Fastqsanger.gz
	SRR6963620_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 562

Similar Datasets

Genomic and epigenomic predictors of response to Guadecitabine in relapsed/refractory Acute Myelogenous Leukemia

Project description:Guadecitabine is a second generation DNA methylation inhibitor with improved pharmacokinetics and clinical activity in relapsed/refractory AML (rrAML). Here we report genome-wide DNA methylation profiles in pre-treatment samples from 116 rrAML patients treated at therapeutic doses of guadecitabine in a phase I/II study. Response rate to guadecitabine was 22 % (16CR, 42 12CRi/CRp). There were no strong mutation or methylation predictors of response. Gene expression defined a subset of patients (~20%) that had (i) high DNMT3B and low CDKN2B, CTCF and CDA expression, (ii) enrichment for KRAS/NRAS mutations, (iii) frequent CpG island hypermethylation (iv) low LINE1 hypomethylation after treatment and (v) resistance to guadecitabine in both phase I (response rate 0 % vs 33 %, p=0.07) and phase II components of the study (response rate 5 % vs. 30 %, p=0.02). Multivariate analysis identified peripheral blood blasts and hemoglobin as predictors of response and cytogenetics, gene expression, RAS mutations and hemoglobin as predictors of survival. Thus, a subset of patients (∿ 20%) with rrAML are unlikely to benefit from single agent guadecitabine. In the remaining 80%, guadecitabine is a viable option with a median survival of ∿ 8 months and a three year survival rate of over 20%.

2019-08-06 | GSE112838 | GEO

Genomic and epigenomic predictors of response to guadecitabine in relapsed/refractory acute myelogenous leukemia.

Project description:BACKGROUND:Guadecitabine is a novel DNA methyltransferase (DNMT) inhibitor with improved pharmacokinetics and clinical activity in a subset of patients with relapsed/refractory acute myeloid leukemia (r/r AML), but identification of this subset remains difficult. METHODS:To search for biomarkers of response, we measured genome-wide DNA methylation, mutations of 54 genes, and expression of a panel of 7 genes in pre-treatment samples from 128 patients treated at therapeutic doses in a phase I/II study. RESULTS:Response rate to guadecitabine was 17% (2 complete remission (CR), 3 CR with incomplete blood count recovery (CRi), or CR with incomplete platelets recovery (CRp)) in the phase I component and 23% (14 CR, 9 CRi/CRp) in phase II. There were no strong mutation or methylation predictors of response. Gene expression clustering defined a subset of patients (~?20%) that had (i) high DNMT3B and low CDKN2B, CTCF, and CDA expression; (ii) enrichment for KRAS/NRAS mutations; (iii) frequent CpG island hypermethylation; (iv) low long interspersed nuclear element 1 (LINE-1) hypomethylation after treatment; and (v) resistance to guadecitabine in both phase I (response rate 0% vs. 33%, p?=?0.07) and phase II components of the study (response rate 5% vs. 30%, p?=?0.02). Multivariate analysis identified peripheral blood (PB) blasts and hemoglobin as predictors of response and cytogenetics, gene expression, RAS mutations, and hemoglobin as predictors of survival. CONCLUSIONS:A subset of patients (~?20%) with r/r AML is unlikely to benefit from guadecitabine as a single agent. In the remaining 80%, guadecitabine is a viable option with a median survival of 8?months and a 2-year survival rate of 21%. TRIAL REGISTRATION:NCT01261312 .

| S-EPMC6647096 | biostudies-literature

DNA methylation of Relapsed/Refractory AML

Project description:DNA methylation of Relapsed/Refractory AML

| PRJNA934390 | ENA

A phase 1 study of guadecitabine plus cisplatin in platinum refractory germ cell tumors [Methylation]

Project description:Germ cell tumors (GCTs) can be cured with cisplatin-based therapy, although a clinically significant number of patents are refractory and die of progressive disease. Based on preclinical studies indicating that refractory testicular GCTs are hypersensitive to hypomethylating agents (HMA), we conducted a phase I trial [NCT02429466] of the next-generation HMA guadecitabine (SGI-110) in combination with cisplatin in patients with recurrent, cisplatin-resistant GCTs. The primary endpoint was safety and toxicity including DLT and MTD. A total of 14 patients were enrolled. The majority of patients were heavily pretreated. MTD was determined to be 30 mg/m2 guadecitabine followed by cisplatin 100 mg/m2. DLTs were neutropenia and thrombocytopenia. Three patients had partial responses by RECIST criteria, two of these patients qualified as complete responses by serum tumor marker criteria with survival of 16 and 26 months. Three patients also had stable disease for an overall response rate of 23% and clinical benefit rate of 46%. Genome-wide analysis pre- and post-guadecitabine indicated dramatic and widespread global DNA demethylation in cell-free plasma samples including in the promoters of genes of cancer related pathways. In summary, the combination of guadecitabine followed by cisplatin was tolerable and demonstrated biological activity in patients with platinum refractory GCTs.

2020-12-25 | GSE152802 | GEO

DNA methylation of Relapsed/Refractory AML

Project description:Genome wide DNA methylation profiling of blood and bone marrow of Pediatric Patients with Relapsed/Refractory Acute Myeloid Leukemia. The Illumina Infinium EPIC Human DNA methylation Beadchip was used to obtain DNA methylation profiles across over 860,000 CpGs.

2023-12-31 | GSE225239 | GEO

ViPOR in Relapsed/Refractory B-Cell Lymphoma

Project description:ViPOR in Relapsed/Refractory B-Cell Lymphoma

| PRJNA1090979 | ENA

Genomic profiling of relapsed and refractory childhood cancers

Project description:Genomic profiling of relapsed and refractory childhood cancers

| PRJNA661354 | ENA

Genomic profiling of relapsed and refractory childhood cancers

Project description:Genomic profiling of relapsed and refractory childhood cancers

| PRJNA661355 | ENA

Altered Expression Profiles of tRNA-derived fragments in relapsed/refractory multiple myeloma

Project description:tRNA related fragments(tRF) and tRNA halves(tiRNA) are novel class of short non-coding RNA derived from tRNAs. Using RNA sequencing, we evaluated the tRFs/tiRNAs expression profiles in relapsed/refractory multiple myeloma and multiple myeloma patients. Bioinformatics analyses indicated that tRFs/tiRNAs may be involved in the progression and drug-resistance of multiple myeloma.

2021-05-19 | GSE171003 | GEO

Pembrolizumab and decitabine for refractory or relapsed acute myeloid leukemia

Project description:Pembrolizumab and decitabine for refractory or relapsed acute myeloid leukemia

| PRJNA800756 | ENA