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ABSTRACT:
PROVIDER: PRJNA1140149 | ENA |
REPOSITORIES: ENA
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Project description:Gene expression in NPM1 wildtype and mutated AML patients with high or low hsa_circ_0075001 expression In acute myeloid leukemia there is growing evidence for splicing pattern deregulation, including differential expression of linear splice isoforms of the commonly mutated gene nucleophosmin (NPM1). In this study, we detect circular RNAs of NPM1 and quantify circRNA hsa_circ_0075001 in a cohort of NPM1 wildtype and mutated acute myeloid leukemia (n=46). Hsa_circ_0075001 expression correlates positively with total NPM1 expression, but is independent of the NPM1 mutational status. High versus low hsa_circ_0075001 expression defines patient subgroups characterized by distinct gene expression patterns, such as lower expression of components of the Toll-like receptor signaling pathway in high hsa_circ_0075001 expression cases. Global evaluation of circRNA expression in sorted healthy hematopoietic controls (n=10) and acute myeloid leukemia (n=10) reveals circRNA transcripts for 47.9% of all highly expressed genes. While circRNA expression correlates globally with parental gene expression, we identify hematopoietic differentiation-associated as well as acute myeloid leukemia subgroup-specific circRNA signatures.
2017-09-22 | GSE104099 | GEO
Project description:Background: MicroRNAs are regulators of gene expression, mainly functioning by decreasing mRNA levels of their multiple targets. Deregulated microRNA expression has been shown for acute myeloid leukemia, a disease also characterized by altered gene expression associated with distinct genomic aberrations such as nucleophosmin (NPM1) mutations. To further illuminate the role of deregulated microRNA and gene expression in cytogenetically normal acute myeloid leukemia with NPM1 mutation, we performed an integrative analysis of microRNA and mRNA expression data sets. Design and Methods: Both microRNA and gene expression profiles were measured in a cohort of 43 adult acute myeloid leukemia patient samples (n=42 cytogenetically normal, n=1 del7q; median age 46 years [range 23-60]) of known NPM1 mutation status (n=23 mutated, n=20 wild-type) and data integratively analyzed. Putative microRNA-mRNA interactions were validated by quantitative RT-PCR, Western Blot and luciferase reporter assays. For selected microRNAs, sensitivity of microRNA-overexpressing cells to cytarabine treatment was tested by FACS viability and cell proliferation assays. Results: Our integrative approach of analyzing both microRNA and gene expression profiles in parallel resulted in a refined list of putative target genes affected by NPM1 mutation-associated microRNA deregulation. Of 177 putative microRNA - target mRNA interactions, we could identify and validate 77 novel candidates with known or potential implication in leukemogenesis, such as IRF2-miR-20a, KIT-miR-20a and MN1-miR-15a. Furthermore, our data showed that deregulated expression of tumor suppressor microRNAs such as miR-29a and miR-30c might contribute to the sensitivity to cytarabine, which is observed in NPM1-mutated acute myeloid leukemia. Conclusions: Overall, our observations highlight that integrative data analysis approaches can improve insights into leukemia biology, and lead to the identification of novel microRNA - target gene interactions of potential relevance for acute myeloid leukemia treatment. MicroRNA and gene expression profiles were measured in a cohort of 43 adult (42 cytogenetically normal and 1 del7q) acute myeloid leukemia patient samples of known NPM1 mutation status (n=23 mutated, n=20 wild-type). This submission represents the mRNA expression component of the study. The miRNA expression data will be deposited as supplementary information along with the accompanying manuscript.
2011-09-11 | E-GEOD-31644 | biostudies-arrayexpress
Project description:NPM1-mutated acute myeloid leukemia (AML) accounts for one third of AML in adults. NPM1-mutated AML maintenance depends on the interaction between mutated NPM1 (NPM1c) and the nuclear exporter Exportin 1 (XPO1). In this work, we show that continous XPO1 inhibition is necessary to achieve stable disruption of the NPM1c-XPO1 interaction and to induce HOX downregulation and differentiation of AML cells with mutated NPM1. In contrast, intermittent XPO1 inhibition only results in minimal transcriptional perturbation and limited antileukemic activity.
2022-09-21 | GSE181176 | GEO
Project description:Clonal evolution in relapsed NPM1 mutated acute myeloid leukemia
| PRJNA203255 | ENA
Project description:The ETCTN 10026 study tested decitabine and ipilimumab for transplant-naive advanced myelodysplastic syndrome/acute myeloid leukemia and relapsed acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation. Using single cell RNA sequencing, determinants of response (higher T/NK to myeloid cell ratio in responders) and resistance (insufficient clearance of AML clones) were identified and pharmacodynamics of decitabine (cytoreduction) and ipilimumab (increase in regulatory T cells) characterized.
2023-10-31 | GSE223844 | GEO