Specific expression of microRNAs and snoRNAs characterize ERG-related B cell precursor acute lymphoblastic leukemia
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PROVIDER: PRJNA316137 | ENA |
REPOSITORIES: ENA
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Project description:ERG-related B cell precursor acute lymphoblastic leukemia (BCP ALL) is a recently described childhood ALL subtype characterized by aberrant ERG protein expression and highly recurrent ERG intragenic deletions. Several studies reported a remarkably favourable outcome for ERG-related BCP-ALL despite a high incidence of apparently inauspicious IKZF1 aberrations. In this study we investigated by integrative genomic analysis the main features of the ERG-related group in a cohort of B-others BCP ALL patients enrolled in the AIEOP ALL 2000 therapeutic protocol. We report a specific microRNA and snoRNA signature that characterizes ERG-related patients with up-regulation of the miR-125b-2 cluster on chromosome 21 and several snoRNAs in the Prader-Willi locus at 15q11.2, including the orphan SNORD116 cluster. Given the current lack of parameters for a comprehensive classification we suggest toexploit the noncoding RNAs signature for differential diagnosis of ERG-related patients.
2017-03-21 | GSE79545 | GEO
Project description:ERG-related B cell precursor acute lymphoblastic leukemia (BCP ALL) is a recently described childhood ALL subtype characterized by aberrant ERG protein expression and highly recurrent ERG intragenic deletions. Several studies reported a remarkably favourable outcome for ERG-related BCP-ALL despite a high incidence of apparently inauspicious IKZF1 aberrations. In this study we investigated by integrative genomic analysis the main features of the ERG-related group in a cohort of B-others BCP ALL patients enrolled in the AIEOP ALL 2000 therapeutic protocol. We report a specific microRNA and snoRNA signature that characterizes ERG-related patients with up-regulation of the miR-125b-2 cluster on chromosome 21 and several snoRNAs in the Prader-Willi locus at 15q11.2, including the orphan SNORD116 cluster. Given the current lack of parameters for a comprehensive classification we suggest toexploit the noncoding RNAs signature for differential diagnosis of ERG-related patients.
2017-03-21 | GSE79546 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2017-03-21 | GSE79547 | GEO
Project description:Specific expression of microRNAs and snoRNAs characterize ERG-related B cell precursor acute lymphoblastic leukemia [mRNA]
| PRJNA316139 | ENA
Project description:Specific expression of microRNAs and snoRNAs characterize ERG-related B cell precursor acute lymphoblastic leukemia [microRNA]
| PRJNA316138 | ENA
Project description:ERG-related leukemia is a B cell precursor acute lymphoblastic leukemia (BCP ALL) subtype characterized by aberrant expression of DUX4 and ERG transcription factors, and highly recurrent ERG intragenic deletions. ERG-related patients have remarkably favorable outcome despite a high incidence of inauspicious IKZF1 aberrations.We describe clinical and genomic features of the ERG-related cases in an unselected cohort of B-other BCP ALL pediatric patients enrolled in the AIEOP ALL 2000 therapeutic protocol. We report a small noncoding RNA signature specific of ERG-related group, with up-regulation of miR-125b-2 cluster on chromosome 21 and several snoRNAs in the Prader-Willi locus at 15q11.2, including the orphan SNORD116 cluster.
| S-EPMC5522075 | biostudies-literature
Project description:High expression of the ETS family transcription factor ERG is associated with poor clinical outcome in acute myeloid leukemia (AML) and acute T-cell lymphoblastic leukemia (T-ALL). In murine models, high ERG expression induces both T-ALL and AML. However, no study to date has defined the effect of high ERG expression on primary human hematopoietic cells. In the present study, human CD34+ cells were transduced with retroviral vectors to elevate ERG gene expression to levels detected in high ERG AML. RNA sequencing was performed on purified populations of transduced cells to define the effects of high ERG on gene expression in human CD34+ cells. Integration of the genome-wide expression data with other data sets revealed that high ERG drives an expression signature that shares features of normal hematopoietic stem cells, high ERG AMLs, early T-cell precursor-ALLs and leukemic stem cell signatures associated with poor clinical outcome. Functional assays linked this gene expression profile to enhanced progenitor cell expansion. These results support a model whereby a stem cell gene expression network driven by high ERG in human cells enhances the expansion of the progenitor pool, providing opportunity for the acquisition and propagation of mutations and the development of leukemia.
2014-10-31 | GSE53665 | GEO
Project description:ERG is an Ets-transcription factor required for normal blood stem cell development. High ERG expression in acute myeloid leukemia (AML) and acute T-cell lymphoblastic leukemia (T-ALL) is associated with a stem cell signature and poor prognosis. In murine over-expression models, human ERG is a potent oncogene that induces both T-ALL and AML. However the functional and molecular consequences of high ERG expression in normal hematopoietic stem/progenitors (HSPCs), and how this contributes to leukemia development, are unknown. Here we show that retroviral transduction of ERG into human CD34+ cells and maintenance of ERG at levels present in high ERG AML results in altered myeloid and T cell differentiation and an increase in the self-renewal capacity of transduced progenitors but not the more primitive stem cell compartment. Integrated analysis of genome-wide expression in high ERG CD34+ and ERG binding profiles in HSPCs revealed that these functional characteristics were accompanied by an expression signature that was enriched in normal HSCs, high ERG AMLs, early T-cell precursor (ETP)-ALLs and leukemic stem cell signatures associated with poor clinical outcome. The proliferative advantage of high ERG progenitors may provide a cellular context for the acquisition and propagation of mutations that contribute to the pathogenesis of leukaemia. RNA sequencing in ERG overexpressing human CD34+ cells
2014-10-31 | E-GEOD-53665 | biostudies-arrayexpress
Project description:Chromosomal rearrangements involving EVI1 (MECOM) define a subtype of acute myeloid leukemia (AML) that is associated with a two-year survival rate of <10%. Gene regulatory functions of EVI1 are largely elusive and no targeted therapeutics exist. We developed experimentally tractable murine and human leukemia models that recapitulate phenotypic and transcriptional features of EVI1-rearranged AML and enable large-scale loss-of-function screens. We characterize EVI1-controlled transcriptional programs in cell culture and in vivo, perform CRISPR screens and identify the ETS-related transcription factor ERG as the only gene that is specifically required for EVI1-driven AML. ERG is transcriptionally activated by EVI1 and overexpressed in EVI1-rearranged AML patients. ERG suppression selectively induces terminal differentiation of leukemia cells. EVI1 becomes dispensable for leukemia cells upon ectopic expression of ERG, indicating that key functions of EVI1 are mediated through aberrant activation of ERG. Interfering with this regulatory axis may therefore provide new entry points for rational therapies.
2022-10-11 | GSE195497 | GEO
Project description:We have identified a specific site in the ERG protein that undergoes post-transcriptional modification. We have mutated this site and generated stably expressing LNCaP cell lines. In this study we evaluated the transcriptional profile induced by ERG in LNCaP stably expressing ERG wild type , ERG mutant or empty vector (EV).
2018-07-31 | GSE71329 | GEO