NPM1 mutation-modulated microRNA-mRNA regulation in acute myeloid leukemia
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE68469 | GEO | 2017/05/03
SECONDARY ACCESSION(S): PRJNA282785
REPOSITORIES: GEO
Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2017-05-03 | E-GEOD-68469 | biostudies-arrayexpress
Project description:Mutation in the nucleophosmin (NPM1) gene is frequent in acute myeloid leukemia (AML). This mutation has remarkable prognostic significance and correlates with distinct biological features. Our data from the sample-paired microRNA (miRNA) and mRNA microarrays of de novo AML patients strongly indicated that miRNA−mRNA regulation (MMR) may be dynamic and can be modulated by NPM1 mutation. We identified 493 NPM1 mutation-modulated MMR pairs by a systematic framework, in which MMR was attenuated specifically in patients carrying NPM1 mutations. The involved miRNAs/mRNAs were associated with cancer and hematological diseases, as well as known functions of NPM1 mutation including cell death and cellular response to therapeutics. The NPM1 mutation modulation could be validated with three approaches, including two independent cohort datasets, a high-throughput dataset derived from cell line-based experiments, and two in vitro models. Our study provides novel biological insights into the role of NPM1 mutation as a modulator of MMR, based on which novel prognostic markers are derived in AML.
2017-05-03 | GSE68466 | GEO
Project description:Mutation in the nucleophosmin (NPM1) gene is frequent in acute myeloid leukemia (AML). This mutation has remarkable prognostic significance and correlates with distinct biological features. Our data from the sample-paired microRNA (miRNA) and mRNA microarrays of de novo AML patients strongly indicated that miRNA−mRNA regulation (MMR) may be dynamic and can be modulated by NPM1 mutation. We identified 493 NPM1 mutation-modulated MMR pairs by a systematic framework, in which MMR was attenuated specifically in patients carrying NPM1 mutations. The involved miRNAs/mRNAs were associated with cancer and hematological diseases, as well as known functions of NPM1 mutation including cell death and cellular response to therapeutics. The NPM1 mutation modulation could be validated with three approaches, including two independent cohort datasets, a high-throughput dataset derived from cell line-based experiments, and two in vitro models. Our study provides novel biological insights into the role of NPM1 mutation as a modulator of MMR, based on which novel prognostic markers are derived in AML.
2017-05-03 | GSE68467 | GEO
Project description:Mutation in the nucleophosmin (NPM1) gene is frequent in acute myeloid leukemia (AML). This mutation has remarkable prognostic significance and correlates with distinct biological features. Our data from the sample-paired microRNA (miRNA) and mRNA microarrays of de novo AML patients strongly indicated that miRNAâmRNA regulation (MMR) may be dynamic and can be modulated by NPM1 mutation. We identified 493 NPM1 mutation-modulated MMR pairs by a systematic framework, in which MMR was attenuated specifically in patients carrying NPM1 mutations. The involved miRNAs/mRNAs were associated with cancer and hematological diseases, as well as known functions of NPM1 mutation including cell death and cellular response to therapeutics. The NPM1 mutation modulation could be validated with three approaches, including two independent cohort datasets, a high-throughput dataset derived from cell line-based experiments, and two in vitro models. Our study provides novel biological insights into the role of NPM1 mutation as a modulator of MMR, based on which novel prognostic markers are derived in AML. Cryopreserved bone marrow cells were obtained from 109 de novo AML patients. Each sample was analyzed with Illumina HumanHT-12 V4.0 expression beadchip.
2017-05-03 | E-GEOD-68466 | biostudies-arrayexpress
Project description:Mutation in the nucleophosmin (NPM1) gene is frequent in acute myeloid leukemia (AML). This mutation has remarkable prognostic significance and correlates with distinct biological features. Our data from the sample-paired microRNA (miRNA) and mRNA microarrays of de novo AML patients strongly indicated that miRNAâmRNA regulation (MMR) may be dynamic and can be modulated by NPM1 mutation. We identified 493 NPM1 mutation-modulated MMR pairs by a systematic framework, in which MMR was attenuated specifically in patients carrying NPM1 mutations. The involved miRNAs/mRNAs were associated with cancer and hematological diseases, as well as known functions of NPM1 mutation including cell death and cellular response to therapeutics. The NPM1 mutation modulation could be validated with three approaches, including two independent cohort datasets, a high-throughput dataset derived from cell line-based experiments, and two in vitro models. Our study provides novel biological insights into the role of NPM1 mutation as a modulator of MMR, based on which novel prognostic markers are derived in AML. Cryopreserved bone marrow cells were obtained from 109 de novo AML patients. Each sample was analyzed with nCounter® Human miRNA Expression Array.
2017-05-03 | E-GEOD-68467 | biostudies-arrayexpress
Project description:NPM1 mutation-modulated microRNA-mRNA regulation in acute myeloid leukemia
| PRJNA282785 | ENA
Project description:SETD2 is the only methyltransferase for H3K36me3, and our previous study has firstly demonstrated that it functioned as one tumor suppressor in hematopoiesis. Consistent with it, SETD2 mutation, which led to its loss of function, was identified in AML. However, the distribution and function of SETD2 mutation in AML remained largely unknown. Herein, we integrated SETD2-mutated AML cases from our center and literature reports, and found that NPM1 mutation was the most common concomitant genetic alteration with SETD2 mutation in AML, with its frequency even higher than MLL rearrangement and AML1-ETO. Though this result indicated the cooperation of SETD2 and NPM1 mutations in leukemogenesis, our functional study showed that SETD2 was required for the proliferation of NPM1-mutated AML cell line OCI-AML3, but not MLL-rearranged AML cell line THP-1, via maintaining its direct target NPM1 expression, which was just opposite to its role of tumor suppressor. Therefore, we speculated that SETD2 possibly had two different faces in distinct subtypes and stages of AML.
| S-EPMC7659109 | biostudies-literature
Project description:Nucleophosmin (NPM1) is a widely expressed nucleocytoplasmic shuttling protein with prominent nucleolar localization. It is estimated that 25-35% of adult patients with acute myeloid leukemia (AML) carry NPM1 mutations. The classic NPM1 type A mutation occurs in exon 12, which accounts for 75-80% of adult patients with NPM1-mutated AML. It produces an additional leucine and valine-rich nuclear export signal (NES) at the C-terminus, and causes aberrant cytoplasmic dislocation of NPM1 protein. Notably, emerging evidence indicates that besides the classic type A mutation, rare mutants occurring in other exons may also lead to the imbalance of the nucleocytoplasmic shuttle of NPM1. Identification of novel non-type A mutants is crucial for the diagnosis, prognosis, risk stratification and disease monitoring of potential target populations. Here we reported a novel NPM1 mutation in exon 5 identified from a de novo AML patient. Similar to the classic type A mutation, the exon 5 mutation had the NPM1 mutant bound to exportin-1 and directed the mutant into the cytoplasm by generating an additional NES sequence, resulting in aberrant cytoplasmic dislocation of NPM1 protein, which could be reversed by exportin-1 inhibitor leptomycin B. Our findings strongly support that besides the exon 12 mutation, the exon 5 mutant is another NPM1 "born to be exported" mutant critical for leukemogenesis. Therefore, similar to the classic type A mutation, the identification of our novel NPM1 mutation is beneficial for clinical laboratory diagnosis, genetic risk assessment and MRD monitoring.
| S-EPMC10548603 | biostudies-literature
Project description:Mutations in the nucleophosmin 1 (NPM1) gene are considered founder mutations in the pathogenesis of acute myeloid leukemia (AML). To characterize the genetic composition of NPM1 mutated (NPM1mut) AML, we assess mutation status of five recurrently mutated oncogenes in 129 paired NPM1mut samples obtained at diagnosis and relapse. We find a substantial shift in the genetic pattern from diagnosis to relapse including NPM1mut loss (n = 11). To better understand these NPM1mut loss cases, we perform whole exome sequencing (WES) and RNA-Seq. At the time of relapse, NPM1mut loss patients (pts) feature distinct mutational patterns that share almost no somatic mutation with the corresponding diagnosis sample and impact different signaling pathways. In contrast, profiles of pts with persistent NPM1mut are reflected by a high overlap of mutations between diagnosis and relapse. Our findings confirm that relapse often originates from persistent leukemic clones, though NPM1mut loss cases suggest a second "de novo" or treatment-associated AML (tAML) as alternative cause of relapse.
| S-EPMC6497712 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2019-05-14 | GSE128604 | GEO