placeholder
and
and

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Proceed order?

Export
Filter
Document type
Language
Year
  • 1
    Language: English
    In: Molecular cancer, 2017-07-19, Vol.16 (1), p.126-126
    Description: Long non-coding RNAs (lncRNAs) play a variety of cellular roles, including regulation of transcription and translation, leading to alterations in gene expression. Some lncRNAs modulate the expression of chromosomally adjacent genes. Here, we assess the roles of the lncRNA CASC15 in regulation of a chromosomally nearby gene, SOX4, and its function in RUNX1/AML translocated leukemia. CASC15 is a conserved lncRNA that was upregulated in pediatric B-acute lymphoblastic leukemia (B-ALL) with t (12; 21) as well as pediatric acute myeloid leukemia (AML) with t (8; 21), both of which are associated with relatively better prognosis. Enforced expression of CASC15 led to a myeloid bias in development, and overall, decreased engraftment and colony formation. At the cellular level, CASC15 regulated cellular survival, proliferation, and the expression of its chromosomally adjacent gene, SOX4. Differentially regulated genes following CASC15 knockdown were enriched for predicted transcriptional targets of the Yin and Yang-1 (YY1) transcription factor. Interestingly, we found that CASC15 enhances YY1-mediated regulation of the SOX4 promoter. Our findings represent the first characterization of this CASC15 in RUNX1-translocated leukemia, and point towards a mechanistic basis for its action.
    Subject(s): Cell Proliferation - genetics ; SOXC Transcription Factors - genetics ; Prognosis ; Humans ; Gene Expression Profiling - methods ; RNA, Long Noncoding - genetics ; YY1 Transcription Factor - genetics ; Promoter Regions, Genetic - genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics ; Animals ; Cell Line, Tumor ; Mice ; Child ; Core Binding Factor Alpha 2 Subunit - genetics ; Gene Expression Regulation, Neoplastic - genetics ; Leukemia, Myeloid, Acute - genetics ; Translocation, Genetic - genetics ; RNA ; Genes ; Genetic transcription ; B-all ; Research ; ETV6-RUNX1 ; Non-coding RNA ; CASC15 ; SOX4
    ISSN: 1476-4598
    E-ISSN: 1476-4598
    Source: BioMedCentral Open Access
    Source: Academic Search Ultimate
    Source: PubMed Central
    Source: DOAJ Directory of Open Access Journals - Not for CDI Discovery
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 2
    Language: English
    In: The Journal of clinical investigation, 2016-04-01, Vol.126 (4), p.1495-1511
    Description: Posttranscriptional control of gene expression is important for defining both normal and pathological cellular phenotypes. In vitro, RNA-binding proteins (RBPs) have recently been shown to play important roles in posttranscriptional regulation; however, the contribution of RBPs to cell specification is not well understood. Here, we determined that the RBP insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) is specifically overexpressed in mixed lineage leukemia-rearranged (MLL-rearranged) B-acute lymphoblastic leukemia (B-ALL), which constitutes a subtype of this malignancy associated with poor prognosis and high risk of relapse. IGF2BP3 was required for the survival of B-ALL cell lines, as knockdown led to decreased proliferation and increased apoptosis. Enforced expression of IGF2BP3 provided murine BM cells with a strong survival advantage, led to proliferation of hematopoietic stem and progenitor cells, and skewed hematopoietic development to the B cell/myeloid lineage. Cross-link immunoprecipitation and high throughput sequencing uncovered the IGF2BP3-regulated transcriptome, which includes oncogenes MYC and CDK6 as direct targets. IGF2BP3 regulated transcripts via targeting elements within 3' untranslated regions (3'UTR), and enforced IGF2BP3 expression in mice resulted in enhanced expression of Myc and Cdk6 in BM. Together, our data suggest that IGF2BP3-mediated targeting of oncogenic transcripts may represent a critical pathogenetic mechanism in MLL-rearranged B-ALL and support IGF2BP3 and its cognate RNA-binding partners as potential therapeutic targets in this disease.
    Subject(s): Insulin-Like Growth Factor Binding Protein 3 - genetics ; RNA-Binding Proteins - genetics ; Cell Proliferation ; Humans ; Hematopoietic Stem Cells - pathology ; Male ; RNA, Neoplasm - metabolism ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - metabolism ; Insulin-Like Growth Factor Binding Protein 3 - metabolism ; Female ; B-Lymphocytes - pathology ; 3' Untranslated Regions ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology ; B-Lymphocytes - metabolism ; Cyclin-Dependent Kinase 6 - genetics ; Cyclin-Dependent Kinase 6 - metabolism ; Hematopoietic Stem Cells - metabolism ; Gene Expression Regulation, Leukemic ; Proto-Oncogene Proteins c-myc - metabolism ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics ; Animals ; Cell Line, Tumor ; Myeloid Cells - metabolism ; RNA, Neoplasm - genetics ; Mice ; Proto-Oncogene Proteins c-myc - genetics ; Myeloid Cells - pathology ; RNA-Binding Proteins - metabolism ; Cell proliferation ; Molecular targeted therapy ; Development and progression ; Genetic aspects ; Acute lymphocytic leukemia ; Binding proteins ; Properties ; Methods ; Proteins ; Medical research ; Flow cytometry ; Laboratories ; Rodents ; Leukemia ; Medical prognosis ; Cell cycle ; Stem cells ; Grants ; Gene expression ; Experiments ; Abridged Index Medicus
    ISSN: 0021-9738
    E-ISSN: 1558-8238
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    Source: PubMed Central
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 3
    Language: English
    In: Cell death and differentiation, 2020-10, Vol.27 (10), p.2749-2767
    Description: The Activation-Induced Cell Death (AICD) is a stimulation-dependent form of apoptosis used by the organism to shutdown T-cell response once the source of inflammation has been eliminated, while allowing the generation of immune memory. AICD is thought to progress through the activation of the extrinsic Fas/FasL pathway of cell death, leading to cytochrome-C release through caspase-8 and Bid activation. We recently described that, early upon AICD induction, mitochondria undergo structural alterations, which are required to promote cytochrome-C release and execute cell death. Here, we found that such alterations do not depend on the Fas/FasL pathway, which is instead only lately activated to amplify the cell death cascade. Instead, such alterations are primarily dependent on the MAPK proteins JNK1 and ERK1/2, which, in turn, regulate the activity of the pro-fission protein Drp1 and the pro-apoptotic factor Bim. The latter regulates cristae disassembly and cooperate with Drp1 to mediate the Mitochondrial Outer Membrane Permeabilization (MOMP), leading to cytochrome-C release. Interestingly, we found that Bim is also downregulated in T-cell Acute Lymphoblastic Leukemia (T-ALL) cells, this alteration favouring their escape from AICD-mediated control.
    Subject(s): Cell biology ; Immune cell death ; Preclinical research
    ISSN: 1350-9047
    E-ISSN: 1476-5403
    Source: Nature Open Access
    Source: PubMed Central
    Source: Alma/SFX Local Collection
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 4
    Language: English
    In: Frontiers in pediatrics, 2020, Vol.8, p.618426-618426
    Subject(s): Pediatrics ; acute leukemia biology ; targeted therapies ; pediatric leukemia ; new drugs ; pediatric acute myeloid leukemia ; pediatric acute lymphoblastic leukemia
    ISSN: 2296-2360
    E-ISSN: 2296-2360
    Source: PubMed Central
    Source: DOAJ Directory of Open Access Journals - Not for CDI Discovery
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 5
    Language: English
    In: Cell death and differentiation, 2020-11, Vol.27 (11), p.3208-3208
    Description: An amendment to this paper has been published and can be accessed via a link at the top of the paper.
    Subject(s): Cell biology ; Immune cell death ; Preclinical research
    ISSN: 1350-9047
    E-ISSN: 1476-5403
    Source: Alma/SFX Local Collection
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 6
    Language: English
    In: Cell reports (Cambridge), 2018-12-11, Vol.25 (11), p.3059-3073.e10
    Description: Mitochondria are key players in the regulation of T cell biology by dynamically responding to cell needs, but how these dynamics integrate in T cells is still poorly understood. We show here that the mitochondrial pro-fission protein Drp1 fosters migration and expansion of developing thymocytes both in vitro and in vivo. In addition, we find that Drp1 sustains in vitro clonal expansion and cMyc-dependent metabolic reprogramming upon activation, also regulating effector T cell numbers in vivo. Migration and extravasation defects are also exhibited in Drp1-deficient mature T cells, unveiling its crucial role in controlling both T cell recirculation in secondary lymphoid organs and accumulation at tumor sites. Moreover, the observed Drp1-dependent imbalance toward a memory-like phenotype favors T cell exhaustion in the tumor microenvironment. All of these findings support a crucial role for Drp1 in several processes during T cell development and in anti-tumor immune-surveillance. [Display omitted] •The pro-fission protein Drp1 sustains correct thymocyte maturation•Drp1 promotes T cell metabolic reprogramming and expansion upon activation•Drp1 allows efficient T cell extravasation from blood and infiltration into tumors•An optimal T cell anti-tumor response requires Drp1 Mitochondria are emerging as key players for optimal T cell functionality. Simula et al. demonstrate that the mitochondrial pro-fission factor Drp1 controls thymocyte maturation and plays multiple roles in mature T cells by promoting their proliferation, migration, and cMyc-dependent metabolic reprogramming upon activation; this activity sustains efficient anti-tumor immune-surveillance.
    Subject(s): cell proliferation ; cell migration ; exhaustion ; tumor immune-surveillance ; thymocytes ; cMyc ; T cells ; metabolic reprogramming ; mitochondrial dynamics ; Drp1 ; Immunologic Surveillance ; Dynamins - metabolism ; Cell Proliferation ; Cell Survival ; Thymocytes - metabolism ; Cell Count ; Homeostasis ; Lymphoid Tissue - metabolism ; Receptors, Antigen, T-Cell ; Proto-Oncogene Proteins c-myc - metabolism ; MAP Kinase Signaling System ; Mice, Knockout ; Lymphocyte Activation - immunology ; Phenotype ; Animals ; T-Lymphocytes - cytology ; T-Lymphocytes - immunology ; Thymocytes - cytology ; Cell Differentiation ; Cell Movement
    ISSN: 2211-1247
    E-ISSN: 2211-1247
    Source: Alma/SFX Local Collection
    Source: DOAJ Directory of Open Access Journals - Not for CDI Discovery
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 7
    Language: English
    In: British journal of haematology, 2017-04, Vol.177 (1), p.116-126
    Description: Summary In children with acute myeloid leukaemia (AML), assessment of initial treatment response is an essential prognostic factor; methods more sensitive than morphology are still under evaluation. We report on the measurement of minimal residual disease (MRD), by multicolour flow‐cytometry in one centralized laboratory, in 142 children with newly diagnosed AML enrolled in the Associazione Italiana di EmatoOncologia Pediatrica‐AML 2002/01 trial. At the end of the first induction course, MRD was 〈0·1% in 69, 0·1–1% in 16 and 〉1% in 51 patients. The 8‐year disease‐free survival (DFS) of 125 children in morphological complete remission and with MRD 〈0·1%, 0·1–1% and ≥1% was 73·1 ± 5·6%, 37·8 ± 12·1% and 34·1 ± 8·8%, respectively (P 〈 0·01). MRD was also available after the second induction course in 92/142 patients. MRD was ≥0·1% at the end of the first induction course in 36 patients; 13 reached an MRD 〈0·1% after the second one and their DFS was 45·4 ± 16·7% vs. 22·8 ± 8·9% in patients with persisting MRD ≥0·1% (P = 0·037). Multivariate analysis demonstrated that MRD ≥0·1% after first induction course was, together with a monosomal karyotype, an independent adverse prognostic factor for DFS. Our results show that MRD detected by flow‐cytometry after induction therapy predicts outcome in patients with childhood AML and can help stratifying post‐remission treatment.
    Subject(s): Minimal residual disease ; Acute myeloid leukaemia ; Paediatric; Risk group ; Flow‐cytometry ; Multivariate Analysis ; Prognosis ; Follow-Up Studies ; Humans ; Child, Preschool ; Immunophenotyping ; Infant ; Male ; Treatment Outcome ; Leukemia, Myeloid, Acute - mortality ; Flow Cytometry ; Leukemia, Myeloid, Acute - diagnosis ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Neoplasm, Residual - diagnosis ; Adolescent ; Survival Analysis ; Leukemia, Myeloid, Acute - drug therapy ; Female ; Child ; Infant, Newborn ; Medical research ; Analysis ; Medicine, Experimental ; Transplantation ; Children ; Chromosomes ; Hematopoietic stem cells ; Diseases
    ISSN: 0007-1048
    E-ISSN: 1365-2141
    Source: Alma/SFX Local Collection
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 8
    Language: English
    In: Leukemia, 2018-05, Vol.32 (5), p.1124-1134
    Description: The somatic translocation t(8;21)(q22;q22)/RUNX1-RUNX1T1 is one of the most frequent rearrangements found in children with standard-risk acute myeloid leukemia (AML). Despite the favorable prognostic role of this aberration, we recently observed a higher than expected frequency of relapse. Here, we employed an integrated high-throughput approach aimed at identifying new biological features predicting relapse among 34 t(8;21)-rearranged patients. We found that the DNA methylation status of patients who suffered from relapse was peculiarly different from that of children maintaining complete remission. The epigenetic signature, made up of 337 differentially methylated regions, was then integrated with gene and protein expression profiles, leading to a network, where cell-to-cell adhesion and cell-motility pathways were found to be aberrantly activated in relapsed patients. We identified most of these factors as RUNX1-RUNX1T1 targets, with Ras Homolog Family Member (RHOB) overexpression being the core of this network. We documented how RHOB re-organized the actin cytoskeleton through its downstream ROCK-LIMK-COFILIN axis: this increases blast adhesion by stress fiber formation, and reduces mitochondrial apoptotic cell death after chemotherapy treatment. Altogether, our data show an epigenetic heterogeneity within t(8;21)-rearranged AML patients at diagnosis able to influence the program of the chimeric transcript, promoting blast re-emergence and progression to relapse.
    Subject(s): Recurrence ; Translocation, Genetic ; Cell Adhesion - genetics ; Blast Crisis - pathology ; Epigenomics ; Leukemia, Myeloid, Acute - pathology ; Humans ; Child, Preschool ; Risk ; Chromosomes, Human, Pair 8 ; rhoB GTP-Binding Protein - metabolism ; Cell Movement - genetics ; Genetic Heterogeneity ; Adolescent ; Cytoskeleton - metabolism ; RUNX1 Translocation Partner 1 Protein - genetics ; Child ; Chromosomes, Human, Pair 21 ; Core Binding Factor Alpha 2 Subunit - genetics ; Leukemia, Myeloid, Acute - genetics
    ISSN: 0887-6924
    E-ISSN: 1476-5551
    Source: Nature Open Access
    Source: Alma/SFX Local Collection
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 9
    Language: English
    In: British journal of haematology, 2018-10, Vol.183 (2), p.298-301
    Description: Table SVI. Putative couples of miRNA and mRNA target with opposite correlated expression and predictive of relapse risk used for network construction.
    Subject(s): miRNA signature ; miRNA ; t(8;21)RUNX1‐RUNX1T1 ; relapse ; paediatric AML ; Gene expression ; Analysis ; MicroRNA
    ISSN: 0007-1048
    E-ISSN: 1365-2141
    Source: Alma/SFX Local Collection
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 10
    Language: English
    In: Haematologica (Roma), 2013-04-01, Vol.98 (4), p.602-610
    Description: MicroRNA-34b down-regulation in acute myeloid leukemia was previously shown to induce CREB overexpression, thereby causing leukemia proliferation in vitro and in vivo. The role of microRNA-34b and CREB in patients with myeloid malignancies has never been evaluated. We examined microRNA-34b expression and the methylation status of its promoter in cells from patients diagnosed with myeloid malignancies. We used gene expression profiling to identify signatures of myeloid transformation. We established that microRNA-34b has suppressor ability and that CREB has oncogenic potential in primary bone marrow cell cultures and in vivo. MicroRNA-34b was found to be up-regulated in pediatric patients with juvenile myelomonocytic leukemia (n=17) and myelodysplastic syndromes (n=28), but was down-regulated in acute myeloid leukemia patients at diagnosis (n=112). Our results showed that hypermethylation of the microRNA-34b promoter occurred in 66% of cases of acute myeloid leukemia explaining the low microRNA-34b levels and CREB overexpression, whereas preleukemic myelodysplastic syndromes and juvenile myelomonocytic leukemia were not associated with hypermethylation or CREB overexpression. In paired samples taken from the same patients when they had myelodysplastic syndrome and again during the subsequent acute myeloid leukemia, we confirmed microRNA-34b promoter hypermethylation at leukemia onset, with 103 CREB target genes differentially expressed between the two disease stages. This subset of CREB targets was confirmed to associate with high-risk myelodysplastic syndromes in a separate cohort of patients (n=20). Seventy-eight of these 103 CREB targets were also differentially expressed between healthy samples (n=11) and de novo acute myeloid leukemia (n=72). Further, low microRNA-34b and high CREB expression levels induced aberrant myelopoiesis through CREB-dependent pathways in vitro and in vivo. In conclusion, we suggest that microRNA-34b controls CREB expression and contributes to myeloid transformation from both healthy bone marrow and myelodysplastic syndromes. We identified a subset of CREB target genes that represents a novel transcriptional network that may control myeloid transformation.
    Subject(s): Humans ; Leukemia, Myeloid - genetics ; Child, Preschool ; Infant ; Gene Expression Profiling ; Promoter Regions, Genetic - genetics ; DNA Methylation ; Cell Transformation, Neoplastic - genetics ; Child ; Infant, Newborn ; Acute Disease ; Cells, Cultured ; Gene Expression Regulation, Leukemic ; Mice, SCID ; Interleukin Receptor Common gamma Subunit - genetics ; Mice, Knockout ; Interleukin Receptor Common gamma Subunit - deficiency ; Cyclic AMP Response Element-Binding Protein - genetics ; Animals ; Adolescent ; HL-60 Cells ; Myeloid Cells - metabolism ; Mice, Inbred NOD ; Mice ; MicroRNAs - genetics ; Myelodysplastic Syndromes - genetics ; Myeloid Cells - pathology ; Original and Brief Reports
    ISSN: 0390-6078
    E-ISSN: 1592-8721
    Source: HighWire Press (Free Journals)
    Source: PubMed Central
    Source: DOAJ Directory of Open Access Journals - Not for CDI Discovery
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...