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GSE87865
Homo sapiens
54 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Although intensification of chemotherapy approaches considerably increased the outcome of pediatric T-cell Acute Lymphoblastic Leukemia (T-ALL) patients, a subgroup of them still experience treatment failure and relapse. In this context, we hypothesized that the Nrf2 signalling and its downstream effectors could be involved in sustain therapy resistance in T-ALL, as previously reported in other cancers. Indeed, in this study we identified the Aldo-Keto Reductase (AKR) enzymes AKR1C1-3, as over-expressed in T-ALL samples from therapy-resistant patients, demonstrating their fundamental role in the control of the response to vincristine (VCR) treatment. In particular, we evidence that the modulation of AKR1C1-3 gene expression and activity is sufficient to strongly affect the sensitivity of T-ALL cell lines and primary cells to VCR treatment, but not to daunorubicin, cytarabine or L-asparaginase. Moreover, we found a correlation between the degree of VCR response and the amount of AKR1Cs expression in patient-derived T-ALL xenografts. Interestingly, we show that daunorubicin and cytarabine are able to induce the over-activation of AKR1C enzymes, thus establishing a potential resistance loop generated by the combination of these drugs during T-ALL treatment.
Publication Title
AKR1C enzymes sustain therapy resistance in paediatric T-ALL.
Sample Metadata Fields
Specimen part, Disease stage
View Samples- Homo sapiens
- 41 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Juvenile myelomonocytic leukemia (JMML) is a very rare and aggressive stem cell disease that mainly occurs in young children. RAS activation constitutes the core component of oncogenic signaling. In addition, the leukemic blasts of a quarter of JMML patients present with monosomy 7 (-7), whereas more than half of the patients show enhanced age-adjusted fetal hemoglobin (HbF) levels. Hematopoietic stem cell transplantation is the current standard of care. This results in an event-free survival of 50 - 60%, indicating that novel molecular driven therapeutic options are urgently needed. Using gene expression profiling in an extensive series of 82 patient samples, we aimed at understanding the molecular biology behind JMML and identified a previously unrecognized molecular subgroup characterized by high LIN28B expression.
Publication Title
LIN28B overexpression defines a novel fetal-like subgroup of juvenile myelomonocytic leukemia.
Sample Metadata Fields
Disease
View Samples- Homo sapiens
- 33 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Anaplastic large-cell lymphoma (ALCL) makes up approximately 15% of paediatric non-Hodgkin's lymphomas of childhood. The vast majority of them is associated with the t(2;5)(p23;q35) translocation that results in the expression of a hybrid oncogenic tyrosine kinase, NPM-ALK. In order to investigate ALCL biological characteristics we used transcriptional profiling approach. Genome-wide gene expression profiling, performed on 23 paediatric ALCL and 12 reactive lymph nodes specimens, showed two novel ALCL subgroups based on their NPM-ALK expression levels (named (ALK low and ALK high). Gene set enrichment analysis revealed, in ALK low samples, a positive enrichment of genes involved in the Interleukin signaling pathway, whereas we found increased expression of genes related to cell cycle progression and division in ALK high tumour samples, such as Aurora Kinase A (AURKA) and B (AURKB). Growth inhibition was observed upon administration of AURKA and AURKB inhibitors Alisertib and Barasertib and it was associated with perturbation of the cell cycle and induction of apoptosis. In conclusion we identified two novel ALCL subgroups, which display unique biological characteristics suggesting sensitivity to distinct targeted therapies.
Publication Title
NPM-ALK expression levels identify two distinct subtypes of paediatric anaplastic large cell lymphoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 28 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Seventeen T-ALL patients out of 120 (14.2%) presented CRLF2 expression 5 times higher than the median (CRLF2-high) with a significantly inferior 5-y EFS and an increased CIR compared to CRLF2-low patients.GEP of 15 T-ALL patients with (CRLF2-high) were compared to 15 CRLF2-low patients. GSEA identified cell cycle deregulating gene sets.
Publication Title
CRLF2 over-expression is a poor prognostic marker in children with high risk T-cell acute lymphoblastic leukemia.
Sample Metadata Fields
Disease
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Identification of relevant subgroups in childhood MDS patients by gene expression analysis and gene involve in progression into AML
Publication Title
Gene expression signatures of pediatric myelodysplastic syndromes are associated with risk of evolution into acute myeloid leukemia.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Circulating microvesicles (MVs) have been described as important players in cell-to-cell communication carrying biological information both in normal and pathologic condition. MVs released by cancer cells may incorporate biomolecules such as active lipids, proteins and RNA, which can be delivered and internalized by recipient cells potentially altering gene expression of receiving cells eventually impacting disease progression. In this study, we took advantage of a leukemia in vitro model to investigate MVs as vehicles of protein coding messages. Leukemic cell lines (K562, REH and SHI-1) carrying recurrent translocations were analyzed. In the leukemic cells these translocations are transcribed into oncogenic fusion transcripts. Here, using gene expression microarrays we monitored leukemic fusion transcripts as hallmarks of leukemic cells transcriptome to track mRNA transfer from parental cells to MVs. Transcriptome analysis of K562 cells and released MVs disclosed MVs as not just small scale cells. In fact, a number of transcripts related to membrane activity, cell surface receptors and extracellular communication were enriched in the MVs pool. On the other hand, sets of transcripts related to the basal cellular functions and transcripts of the BCR-ABL oncogenic pathway downstream of the fusion protein were detected in MVs as well as in parental K562 cells. Moreover, through co-culture analyses uptake of leukemic MVs in receiving cells was confirmed and an MV-dosage dependent increase of target cell proliferation was demonstrated.
Publication Title
Expression Profiling of Circulating Microvesicles Reveals Intercellular Transmission of Oncogenic Pathways.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Increased CREB levels and upregulation of its target genes expression resulted in increased myelopoiesis and colony formation.
Publication Title
MicroRNA-34b promoter hypermethylation induces CREB overexpression and contributes to myeloid transformation.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Glioblastoma (GBM) is the most devastating tumour of the brain, endowed with a fatal prognosis. Indeed, the complete eradication of cancer cell disseminated outside the GBM mass still remains a crucial issue. Given the reported strong association existing between Annexin 2A (ANXA2) expression and cell dissemination in many cancers, we evaluated the effects exerted by the modulation of ANXA2 levels in GBM cells and assessed its potential in predicting patient outcome. Here, we show that expression of ANXA2 positively correlates with metastatic gene signatures and demonstrates to be prognostic by itself. Indeed, we prove that ANXA2 is involved in cell migration, invasion, cytoskeletal remodeling and proliferation in GBM cells. Moreover, we were able to construct a gene signature representative of ANXA2 inhibition, which showed a significant prognostic potential in different GBM patient cohorts.
Publication Title
Annexin 2A sustains glioblastoma cell dissemination and proliferation.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 1 Downloadable Sample
- Affymetrix Clariom S Human array (clariomshuman)
Description
HIF-1 plays a crucial role in sustaining glioblastoma (GBM) cell growth and the maintenance of their undifferentiated phenotype. However, HIF-1 has been suggested to interplay with Wnt signaling components, thus activating a neuronal differentiation process in both GBM and normal brain. Here, we show that a -catenin/TCF1/HIF-1 complex directly controls the transcription of neuronal differentiation genes in hypoxia. Conversely, at higher oxygen levels, the increased expression of TCF4 exerts a transcriptional inhibitory function on the same genomic regions, thus counteracting differentiation. Moreover, we demonstrate the existence of a positive correlation between HIF-1, TCF1 and neuronal phenotype in GBM tumors, accompanied by the over-expression of several Wnt signaling components, finally impacting on patient prognosis. In conclusion, we unveil a mechanism by which TCF1 and HIF-1 induce a reminiscent neuronal differentiation of hypoxic GBM cells, which is hampered, in normoxia, by high levels of TCF4, thus de facto sustaining cell aggressiveness.
Publication Title
HIF-1α/Wnt signaling-dependent control of gene transcription regulates neuronal differentiation of glioblastoma stem cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
phenotypic reprogramming ability of teh zebtafish brain microenviroment on GBM derived cells controlled by the activation of endogenous Wnt pathway
Publication Title
Wnt activation promotes neuronal differentiation of glioblastoma.
Sample Metadata Fields
Specimen part, Time
View Samples