Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

REPROGRAMMING IDENTIFIES FUNCTIONALLY DISTINCT STAGES OF CLONAL EVOLUTION IN MYELODYSPLASTIC SYNDROMES

ABSTRACT: REPROGRAMMING IDENTIFIES FUNCTIONALLY DISTINCT STAGES OF CLONAL EVOLUTION IN MYELODYSPLASTIC SYNDROMES

PROVIDER: PRJNA533068 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR8905800_1.fastq.gz	Fastqsanger.gz
	SRR8905800_2.fastq.gz	Fastqsanger.gz
	SRR8905810_1.fastq.gz	Fastqsanger.gz
	SRR8905810_2.fastq.gz	Fastqsanger.gz
	SRR8905801_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 24

Similar Datasets

Reprogramming identifies functionally distinct stages of clonal evolution in myelodysplastic syndromes.

Project description:Myeloid neoplasms, including myelodysplastic syndromes (MDS), are genetically heterogeneous disorders driven by clonal acquisition of somatic mutations in hematopoietic stem and progenitor cells (HPCs). The order of premalignant mutations and their impact on HPC self-renewal and differentiation remain poorly understood. We show that episomal reprogramming of MDS patient samples generates induced pluripotent stem cells from single premalignant cells with a partial complement of mutations, directly informing the temporal order of mutations in the individual patient. Reprogramming preferentially captured early subclones with fewer mutations, which were rare among single patient cells. To evaluate the functional impact of clonal evolution in individual patients, we differentiated isogenic MDS induced pluripotent stem cells harboring up to 4 successive clonal abnormalities recapitulating a progressive decrease in hematopoietic differentiation potential. SF3B1, in concert with epigenetic mutations, perturbed mitochondrial function leading to accumulation of damaged mitochondria during disease progression, resulting in apoptosis and ineffective erythropoiesis. Reprogramming also informed the order of premalignant mutations in patients with complex karyotype and identified 5q deletion as an early cytogenetic anomaly. The loss of chromosome 5q cooperated with TP53 mutations to perturb genome stability, promoting acquisition of structural and karyotypic abnormalities. Reprogramming thus enables molecular and functional interrogation of preleukemic clonal evolution, identifying mitochondrial function and chromosome stability as key pathways affected by acquisition of somatic mutations in MDS.

| S-EPMC6624967 | biostudies-literature

REPROGRAMMING IDENTIFIES FUNCTIONALLY DISTINCT STAGES OF CLONAL EVOLUTION IN MYELODYSPLASTIC SYNDROMES

Project description:As part of this study, we isolated induced pluripotent stem cells (iPSCs) from a patient with TP53-mutant MDS and identified loss of chromosome 5q as a cooperating genetic event. Using RNA sequencing we found that loss of chromosome 5q dysregulates genes that maintain chromosome stability, predisposing TP53-mutant cells to chromosomal rearrangements and progression to complex karyotype.

2019-04-17 | GSE129851 | GEO

ZRSR2 mutant myelodysplastic syndromes

Project description:ZRSR2 mutant myelodysplastic syndromes

| PRJNA671387 | ENA

ZRSR2 mutant myelodysplastic syndromes

Project description:ZRSR2 mutant myelodysplastic syndromes

| PRJNA671388 | ENA

Oxidative stress in myelodysplastic syndromes

Project description:Control of oxidative stress in the bone marrow (BM) is key for maintaining the balance between self-renewal, proliferation, and differentiation of hematopoietic cells. Breakdown of this regulation can lead to diseases characterized by BM failure such as the myelodysplastic syndromes (MDS). To better understand the role of oxidative stress in MDS development, we compared protein carbonylation as an oxidative stress marker in BM of patients with MDS and control subjects, and also patients with MDS under treatment with the iron chelator deferasirox.

2019-10-30 | PXD013609 | Pride

Affymetrix SNP6.0 microarray data - Myelodysplastic syndromes

Project description:Mutations in the TET2 gene are frequent in myeloid disease, although their biological and prognostic significance remains unclear. We analyzed 355 patients with myelodysplastic syndromes using ‘Next-Generation’ sequencing (NGS) for TET2 aberrations; 91 of whom were also subjected to SNP6 array karyotyping. Seventy-one TET2 mutations, with a relative mutation abundance (RMA) ≥10%, were identified in 39 of 320 (12%) MDS and 16 of 35 (46%) CMML patients (p<0.001). Interestingly, 4 patients had multiple mutations likely to exist as independent clones or on alternate alleles, suggestive of clonal evolution. ‘Deeper’ sequencing of 96 patient samples identified 4 additional mutations (RMA 3%-6.3%). Importantly, TET2 mutant clones were also found in T cells in addition to CD34+ and total bone-marrow cells (23.5%, 38.5% and 43% RMA respectively). Only 20% of the TET2-mutated patients showed loss of heterozygosity at the TET2 locus. There was no difference in the frequency of genome-wide aberrations, TET2 expression or the JAK2V617F 46/1 haplotype between TET2-mutated and non-mutated patients. There was no significant prognostic association between TET2 mutations and WHO subtypes, IPSS score, cytogenetic status, or transformation to AML. On multivariate analysis, age (>50yrs) was associated with a higher incidence of TET2 mutation (p=0.02). Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from bone marrow or peripheral blood samples. Copy number and acquired UPD analysis of Affymetrix SNP 6.0 arrays was performed for 91 cases with Myelodysplastic syndromes.

2010-07-30 | E-GEOD-23300 | biostudies-arrayexpress

Clonal evolution in myelodysplastic syndromes.

Project description:Cancer development is a dynamic process during which the successive accumulation of mutations results in cells with increasingly malignant characteristics. Here, we show the clonal evolution pattern in myelodysplastic syndrome (MDS) patients receiving supportive care, with or without lenalidomide (follow-up 2.5-11 years). Whole-exome and targeted deep sequencing at multiple time points during the disease course reveals that both linear and branched evolutionary patterns occur with and without disease-modifying treatment. The application of disease-modifying therapy may create an evolutionary bottleneck after which more complex MDS, but also unrelated clones of haematopoietic cells, may emerge. In addition, subclones that acquired an additional mutation associated with treatment resistance (TP53) or disease progression (NRAS, KRAS) may be detected months before clinical changes become apparent. Monitoring the genetic landscape during the disease may help to guide treatment decisions.

| S-EPMC5530598 | biostudies-literature

Invariant patterns of clonal succession determine specific clinical features of Myelodysplastic syndromes (MDS)

Project description:Invariant patterns of clonal succession determine specific clinical features of Myelodysplastic syndromes (MDS)

| PRJNA565454 | ENA

Invariant patterns of clonal succession determine specific clinical features of Myelodysplastic syndromes (MDS)

Project description:Invariant patterns of clonal succession determine specific clinical features of Myelodysplastic syndromes (MDS)

| PRJNA565455 | ENA

The National Myelodysplastic Syndromes (MDS) Study

Project description:The National Myelodysplastic Syndromes (MDS) Study

| PRJNA783118 | ENA