We examined if pediatric AMLs rank-ordered according to C/EBP expression showed the activation of similar pathways. AML samples were dichotomized into groups including the upper quartile (Q1) and the lower three quartiles (Q2-4) according to their C/EBP expression values. Moreover, AML samples were associated to French-American-British (FAB) classification.
CREB engages C/EBPδ to initiate leukemogenesis.
Specimen part, Disease
View SamplesTo examine the role of CREB overexpression in hematopoiesis, we created a model of leukemia in zebrafish by overexpressing the human CREB in the myeloid hematopoietic lineage. Whole transcriptome analysis of kidney-marrow revealed 171 genes differently expressed between CREB- and control-zebrafish (five per group). Interestingly, the integration of this signature with human deposited data revealed that this tumor resembled a human AML at transcriptome level.
CREB engages C/EBPδ to initiate leukemogenesis.
Specimen part
View SamplesIncreased CREB levels and upregulation of its target genes expression resulted in increased myelopoiesis and colony formation.
MicroRNA-34b promoter hypermethylation induces CREB overexpression and contributes to myeloid transformation.
Specimen part, Disease, Disease stage, Subject
View SamplesZNF521 is a multiple zinc finger transcription factor previously identified because abundantly and selectively expressed in normal CD34+ hematopoietic stem and progenitor cells. From microarray datasets, aberrant expression of ZNF521 has been reported in both pediatric and adult acute myeloid leukemia (AML) patients with MLL gene rearrangements. However, a proper validation of microarray data is lacking, likewise ZNF521 contribution in MLL-rearranged AML is still uncertain. In this study, we show that ZNF521 is significantly upregulated in MLL translocated AML patients from a large pediatric cohort, regardless of the type of MLL translocations such as MLL-AF9, MLL-ENL, MLL-AF10 and MLL-AF6 fusion genes. Our in vitro functional studies demonstrate that ZNF521 play a critical role in the maintenance of the undifferentiated state of MLL-rearranged cells. Furthermore, analysis of the ZNF521 gene promoter region shows that ZNF521 is a direct downstream target of both MLL-AF9 and MLL-ENL fusion proteins. Gene expression profiling of MLL-AF9-rearranged THP-1 cells after depletion of ZNF521 reveals correlation with several expression signatures including stem cell-like and MLL fusion dependent programs. These data suggest that MLL fusion proteins activate ZNF521 expression to maintain the undifferentiated state and contribute to leukemogenesis.
ZNF521 sustains the differentiation block in MLL-rearranged acute myeloid leukemia.
Specimen part, Cell line
View SamplesWe examined if the minimal residual disease (MRD) and the Allelic Ratio (AR) of FLT3 internal tandem duplication (ITD) mutated patients may be prognostic factors. We correlated these parameters both with event free survival (EFS), with incidence of relapse and with gene expression profile (GEP). GEP showed that patients with high-ITD-AR or persistent MRD had different expression profiles. Results indicated that the ITD-AR levels and the MRD after I induction course are associated with transcriptional oncogenic profiles, which highlight differences in epigenetic control that may explain the variability in outcome among FLT3-ITD patients
Characterization of children with FLT3-ITD acute myeloid leukemia: a report from the AIEOP AML-2002 study group.
Specimen part, Disease
View SamplesSummary:
HCaRG increases renal cell migration by a TGF-alpha autocrine loop mechanism.
No sample metadata fields
View SamplesHEK293 cells were transfected with control plasmid (pcDNAI/Neo;Invitrogen) or with the plasmid encoding HCaRG. Stable transfectants were synchronized and grown in the presence of 10% FBS for 48 h. Total RNAs were purified with the mini RNeasy kit (Qiagen).
HCaRG increases renal cell migration by a TGF-alpha autocrine loop mechanism.
No sample metadata fields
View SamplesThe SCL and LMO1 oncogenic transcription factors reprogram thymocytes into self-renewing pre-leukemic stem cells (pre-LSCs). Here we report that SCL directly interacts with LMO1 to activate the transcription of a self-renewal program coordinated by LYL1.
SCL, LMO1 and Notch1 reprogram thymocytes into self-renewing cells.
Age, Specimen part
View SamplesThe Drosophila TRIM-NHL protein Brain tumor (Brat) plays important roles during early embryogenesis, in cell fate decisions, during neurogenesis and in mature neurons. Brat is an RNA-binding protein and functions as translational repressor. However, which RNAs Brat regulates and how RNA-binding specificity is achieved, is unknown. Using RNA-Immunoprecipitation we identify Brat-bound mRNAs in Drosophila embryos and define a consensus binding motif.
The Crystal Structure of the NHL Domain in Complex with RNA Reveals the Molecular Basis of Drosophila Brain-Tumor-Mediated Gene Regulation.
Specimen part
View SamplesBackground Alternative splicing (AS) is a central mechanism of genetic regulation which modifies the sequence of RNA transcripts in higher eukaryotes. AS has been shown to increase both the variability and diversity of the cellular proteome by changing the composition of resulting proteins through differential choice of exons to be included in mature mRNAs. Results In the present study, alterations to the global RNA splicing landscape of cellular genes upon viral infection were investigated through high-throughput RNA sequencing (RNA-seq) studies using mammalian reovirus as a model. Our study provides the first comprehensive portrait of global changes in the RNA splicing signatures that occur in eukaryotic cells following infection with a human virus. We identify modifications in the AS patterns of 240 cellular transcripts frequently involved in the regulation of gene expression and RNA metabolism. A significant number of the modified transcripts are also encoded by genes with important roles in viral infection/immunity. These modifications are expected to alter the functions of many cellular proteins. Finally, we used RT-PCR analysis in order to experimentally validate differential modifications in alternative splicing patterns that were observed through RNA-seq studies. Conclusion The present study demonstrated that viral infection can extensively modify the splicing patterns of numerous cellular transcripts. These findings provide additional insights into the complexity of virus-host interactions as these splice variants expand proteome diversity and function during viral infection. Finally, these data open new avenues of research for a better understanding of post-transcriptional events during virus infection and possible new targets toward the development of antiviral agents. Overall design: mRNAs were isolated from L929 mouse cell line, 14 hours after infection with T3D-S Reovirus or T3D-S Mutant reovirus at a MOI of 50. Control cells were uninfected. The resulting libraries were multiplexed and paired-end sequenced using Illumina HiSeq. Gene expression and alternative splicing were caracterized using Bowtie and RSEM.
Global Profiling of the Cellular Alternative RNA Splicing Landscape during Virus-Host Interactions.
Specimen part, Cell line, Subject
View Samples