Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA88009 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Affymetrix SNP array data for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS)
| PRJNA207107 | ENA
Project description:This study describes a recurrent dicentric chromosome formed by telomere fusion between chromosome 20 and chromosome 22 in myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML). This is the first description of a recurrent telomere fusion event in myeloid malignancy. The derivative chromosome is further characterised by the presence of nucleolus organiser region material from the chromosome 22 short arm, loss of the putative tumour suppressor gene at 20q12 and secondary rearrangements including gain or amplification of 20q material adjacent to the deletion encompassing 20q12. The presence of residual telomere sequence at the site of translocation in three of the four cases is compelling support for telomere fusion, and supports previous evidence that over half of dicentric chromosomes involving 20q are produced by telomere fusion events. We propose that the sequence of events producing this chromosome abnormality is initial formation of an unstable dicentric chromosome by 20q and 22p telomere fusion, followed by breakage-fusion-bridge cycles causing 20q12 deletion and 20q11.2 gain which provide a growth advantage to the cell. Selection of these clones contributes to leukaemogenesis. Finding recurrent patterns in the complex genome reorganisation events which characterise poor prognosis, complex karyotype AML and MDS will help us understand the mechanisms and oncogenic driver mutations in these poorly understood malignancies. The sample consists of leukaemia specimens from three different cases of AML and MDS. The consistent feature was the presence of a dicentric chromosome formed from chromosomes 20 and 22.
2016-06-30 | E-GEOD-64050 | biostudies-arrayexpress
Project description:The diagnosis of myelodysplastic syndromes (MDS) remains problematic due to the subjective nature of morphological assessment. The reported high frequency of somatic mutations and increased structural variants by array-based cytogenetics have provided potential objective markers of disease however this has been complicated by reports of similar abnormalities in the healthy population. We aimed to identify distinguishing features between those with early MDS and reported healthy individuals by characterising 69 patients who, following a non-diagnostic marrow, developed progressive dysplasia or acute myeloid leukaemia (AML). Targeted sequencing and array based cytogenetics identified a driver mutation and/or structural variant in 91% (63/69) of pre-diagnostic samples with the mutational spectrum mirroring that in the MDS population. When compared with the reported healthy population the mutations detected had significantly greater median variant allele fraction (40% vs 9-10%) and occurred more commonly with additional mutations (≥2 mutations 64% vs. 8%). Furthermore mutational analysis identified a high-risk group of patients with shorter time to disease progression and poorer overall survival. The mutational features in our cohort are distinct from those seen in the healthy population and, even in the absence of definitive disease, can predict outcome. Early detection may allow consideration of intervention in poor risk patients. We performed array based cytogenetics using HumanCytoSNP-12 (Illumina) on 69 patients diagnosed with acute myeloid leukaemia or myelodysplastic syndrome who had a previously non-diagnostic sample. SNP array analysis was performed on all diagnostic samples. In those with a documented abnormality, SNP-A was performed on the corresponding pre-diagnostic sample (n=32).
2015-09-17 | E-GEOD-73074 | biostudies-arrayexpress
Project description:We assessed lineage involvement by NUP98 translocations in myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and T-cell acute lymphoblastic leukemia (T-ALL). Single cell analysis by FICTION (Fluorescence Immunophenotype and Interphase Cytogenetics as a Tool for Investigation of Neoplasms) showed that NUP98-translocations with various partners, i.e. NSD1, DDX10, RAP1GDS1, and LNP1, always affected a CD34+/CD133+ hematopoietic precursor. Interestingly, in MDS/AML myelomonocytes, erythroid cells, B- and T- lymphocytes belonged to the abnormal clone, while in T-ALL only CD7+/CD3+ cells were involved. The partner did not appear to play a major role in determining the leukemia phenotype as shown in AML and T-ALL with the same NUP98-RAP1GDS1 fusion. Additional hits, namely mutations of FLT3 and CEBPA in MDS/AML and mutation of NOTCH1 plus MYB duplication in T-ALL, were identified in leukemias with, respectively, myeloid or T-lymphoid phenotype. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved diagnostic bone marrow or peripheral blood samples. Copy number and Copy neutral LOH analysis of with Affymetrix Cytogenetic 2.7 and Cytoscan HD SNP arrays was performed on 6 NUP98 rearranged leukemias.
2014-08-26 | E-GEOD-60733 | biostudies-arrayexpress
Project description:Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) harboring both inv(3)/t(3;3) and monosomy 7 (-7) are highly aggressive myeloid cancers whose molecular pathogenesis and therapeutic vulnerability remain elusive. High throughput drug screens, CUT&Tag/RNA sequence and functional assays using human MDS/AML cells revealed that EZH2 inhibitors efficiently induce apoptosis preferentially in MDS/AML with inv(3)/t(3;3) and -7 through activation of GADD45γ-p38-p53 axis. EVI1 activated in 3q-rearranged MDS/AML was responsible for GADD45γ silencing by direct binding to its consensus sequence within GADD45γ promoter and recruitment of PRC2 complex via interaction with EZH2, which can be therapeutically targeted by EZH2 inhibition. MDS/AML with inv(3)/t(3;3) and -7 showed preferential sensitivity to EZH2 inhibition in both mouse model and patient samples. Thus, MDS/AML cells with inv(3)/t(3;3) and -7 possess apoptosis evasion mechanism through EVI1-PRC2-mediated repression of GADD45γ-p38-p53 axis, which is a potential therapeutic vulnerability in MDS/AML patients with these high-risk cytogenetic lesions.
2024-06-29 | GSE270760 | GEO
Project description:We assessed lineage involvement by NUP98 translocations in myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and T-cell acute lymphoblastic leukemia (T-ALL). Single cell analysis by FICTION (Fluorescence Immunophenotype and Interphase Cytogenetics as a Tool for Investigation of Neoplasms) showed that NUP98-translocations with various partners, i.e. NSD1, DDX10, RAP1GDS1, and LNP1, always affected a CD34+/CD133+ hematopoietic precursor. Interestingly, in MDS/AML myelomonocytes, erythroid cells, B- and T- lymphocytes belonged to the abnormal clone, while in T-ALL only CD7+/CD3+ cells were involved. The partner did not appear to play a major role in determining the leukemia phenotype as shown in AML and T-ALL with the same NUP98-RAP1GDS1 fusion. Additional hits, namely mutations of FLT3 and CEBPA in MDS/AML and mutation of NOTCH1 plus MYB duplication in T-ALL, were identified in leukemias with, respectively, myeloid or T-lymphoid phenotype.
2014-08-26 | GSE60733 | GEO
Project description:<p>We used massively parallel sequencing technology to sequence the genomic DNA of tumor cells (leukemic bone marrow) and normal cells (skin biopsy) obtained from patients with Acute Myeloid Leukemia (AML). Patients had either de novo AML (AML with no prior diagnosis of a hematologic disease or exposure to chemotherapy), secondary AML (occurring after a prior diagnosis of myelodysplastic syndromes (MDS)), or therapy-related AML (occurring after exposure to prior chemotherapy). We identified somatic mutations in the tumor genomes, including single nucleotide variants, insertions, deletions, and structural variants.</p>
| phs000159 | dbGaP
Project description:Aplastic anaemia (AA) is a form of bone marrow failure (BMF) resulting in significant cytopenias and may progress with clonal evolution to myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML). MicroRNA expression is dysregulated in MDS/AML but there are limited studies on its role in the pathogenesis of AA. Using stored BM samples (n=81) from 2006-2019 from 52 patients, we demonstrate key differences in miRNA expression between AA patients at diagnosis and de novo MDS patients (n=21). The five most significantly upregulated miRNA in MDS patients (downregulated in AA) were miR-130a-3p, miR-221-3p, miR-126-3p, miR-27b-3p and miR-196b-5p (adj p<0.001). However, at the time of AA clonal progression to secondary MDS/AML, no significant miRNA differences were identified suggesting that the underlying mechanistic pathways are similar between AA progression to MDS/AML and de novo MDS. At diagnosis, miR-127-3p, miR-1271-5p, miR-301b-5p, miR-3934-5p and miR-4531 (adj p=0.081) were upregulated in those whose AA eventually progressed in comparison to those without eventual clonal progression. Using KEGG pathway analysis derived from miRPathDBv2.0, cytokine-cytokine receptor interaction, TGF-, MAP kinase, prolactin, Hippo, neurotrophin and FOXO signalling pathways were enriched in AA patients with clonal progression to MDS/AML; these pathways were similarly enriched in the de novo MDS cohort. These studies highlight the differing miRNA expression profiles in AA and MDS and in AA clonal evolution to MDS/AML.
2023-09-02 | GSE242216 | GEO
Project description:This is a first-in-human, multi-center, open-label clinical study with separate dose escalation (Phase 1) and expansion (Phase 2) stages to assess preliminary safety, tolerability, and efficacy of the second generation oral XPO1 inhibitor KPT-8602 in participants with relapsed/refractory multiple myeloma (MM), metastatic colorectal cancer (mCRC), metastatic castration resistant prostate cancer (mCRPC), higher risk myelodysplastic syndrome (HRMDS), acute myeloid leukemia (AML) and newly diagnosed intermediate/high-risk MDS.
Dose escalation and dose expansion may be included for all parts of the study as determined by ongoing study results.
| 2205768 | ecrin-mdr-crc
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 Direct comparison of DNA methylation in bone marrow samples from patients with Myelodysplastic syndrome or secondary Acute Myeloid Leukemia (AML) at baseline and after in vivo treatment with 5-azacytidine + etinostat. A comparison to de novo normal karyotype AML was also performed. Two control groups were included: one consisting of 8 CD34+ bone marrow samples from healthy donors and a second one consisting of matched CD34+ and CD34- fractions from the bone marrows of 4 healthy donors.
2010-05-15 | E-GEOD-17328 | biostudies-arrayexpress