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: Leukemia, 2014-05, Vol.28 (5), p.1132-1134
    Subject(s): Core Binding Factors - genetics ; Leukemia, Myeloid, Acute - diagnosis ; Prognosis ; Leukemia, Myeloid, Acute - pathology ; Humans ; Proto-Oncogene Proteins c-kit - genetics ; Mutation ; Leukemia, Myeloid, Acute - genetics ; Development and progression ; Transcription factors ; Genetic aspects ; Gene mutations ; Health aspects ; Leukemia in children
    ISSN: 0887-6924
    E-ISSN: 1476-5551
    Source: Nature Open Access
    Source: Academic Search Ultimate
    Source: Alma/SFX Local Collection
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 2
    Language: English
    In: Leukemia, 2017-01, Vol.31 (1), p.18-25
    Description: Recurrent molecular markers have been routinely used in acute myeloid leukemia (AML) for risk assessment at diagnosis, whereas their post-induction monitoring still represents a debated issue. We evaluated the prognostic value and biological impact of minimal residual disease (MRD) and of the allelic ratio (AR) of FLT3-internal-tandem duplication (ITD) in childhood AML. We retrospectively screened 494 children with de novo AML for FLT3-ITD mutation, identifying 54 harboring the mutation; 51% of them presented high ITD-AR at diagnosis and had worse event-free survival (EFS, 19.2 versus 63.5% for low ITD-AR, 〈0.05). Forty-one percent of children with high levels of MRD after the 1st induction course, measured by a patient-specific real-time-PCR, had worse EFS (22.2 versus 59.4% in low-MRD patients, P〈0.05). Next, we correlated these parameters with gene expression, showing that patients with high ITD-AR or persistent MRD had characteristic expression profiles with deregulated genes involved in methylation and acetylation. Moreover, patients with high CyclinA1 expression presented an unfavorable EFS (20.3 versus 51.2% in low CyclinA1 group, P〈0.01). Our results suggest that ITD-AR levels and molecular MRD should be considered in planning clinical management of FLT3-ITD patients. Different transcriptional activation of epigenetic and oncogenic profiles may explain variability in outcome among these patients, for whom novel therapeutic approaches are desirable.
    Subject(s): fms-Like Tyrosine Kinase 3 - genetics ; Disease-Free Survival ; Leukemia, Myeloid, Acute - diagnosis ; Prognosis ; Epigenesis, Genetic - genetics ; Humans ; Child, Preschool ; Retrospective Studies ; Gene Expression Regulation, Leukemic ; Child ; Neoplasm, Residual - genetics ; Leukemia, Myeloid, Acute - genetics ; Molecular targeted therapy ; Gene mutations ; Gene expression ; Health aspects ; Innovations
    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 ...
  • 3
    Language: English
    In: Leukemia, 2017-04, Vol.31 (4), p.974-977
    Subject(s): Daunorubicin - therapeutic use ; Prognosis ; Cytarabine - therapeutic use ; Humans ; Up-Regulation - genetics ; Methotrexate - therapeutic use ; Mutation - genetics ; Cyclophosphamide - therapeutic use ; Down-Regulation - genetics ; Nuclear Pore Complex Proteins - genetics ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Mercaptopurine - therapeutic use ; Oncogene Proteins, Fusion - genetics ; Vincristine - therapeutic use ; Leukemia, Myeloid, Acute - drug therapy ; Biomarkers, Tumor - genetics ; Asparaginase - therapeutic use ; Prednisone - therapeutic use ; Leukemia, Myeloid, Acute - genetics ; Translocation, Genetic - 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 ...
  • 4
    Language: English
    In: Leukemia, 2016-09-01, Vol.30 (9), p.1887
    Description: cAMP response element binding protein (CREB) is frequently overexpressed in acute myeloid leukemia (AML) and acts as a proto-oncogene; however, it is still debated whether such overactivation alone is able to induce leukemia as its pathogenetic downstream signaling is still unclear. We generated a zebrafish model overexpressing CREB in the myeloid lineage, which showed an aberrant regulation of primitive hematopoiesis, and in 79% of adult CREB-zebrafish a block of myeloid differentiation, triggering to a monocytic leukemia akin the human counterpart. Gene expression analysis of CREB-zebrafish revealed a signature of 20 differentially expressed human homologous CREB targets in common with pediatric AML. Among them, we demonstrated that CREB overexpression increased CCAAT-enhancer-binding protein-[delta] (C/EBP[delta]) levels to cause myeloid differentiation arrest, and the silencing of CREB-C/EBP[delta] axis restored myeloid terminal differentiation. Then, C/EBP[delta] overexpression was found to identify a subset of pediatric AML affected by a block of myeloid differentiation at monocytic stage who presented a significant higher relapse risk and the enrichment of aggressive signatures. Finally, this study unveils the aberrant activation of CREB-C/EBP[delta] axis concurring to AML onset by disrupting the myeloid cell differentiation process. We provide a novel in vivo model to perform high-throughput drug screening for AML cure improvement.
    Subject(s): Pediatrics ; Analysis ; Cyclic adenylic acid ; Genetic aspects ; Gene expression ; Cell differentiation ; Protein binding
    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 ...
  • 5
    Language: English
    In: Leukemia, 2008-12, Vol.22 (12), p.2217-2225
    Description: The inducible cyclic AMP (cAMP) early repressor (ICER) and cAMP response element-binding protein (CREB) are transcriptional regulators of the cAMP-mediated signaling pathway. CREB has been demonstrated to be upregulated in the majority of childhood leukemias contributing to disease progression, whereas ICER, its endogenous repressor, was found to be downregulated. Our research focus has been the function of restored ICER expression. ICER exogenously expressed in cell lines decreases CREB protein level and induces a lowered clonogenic potential in vitro. It decreases the ability of HL60 to invade the extramedullary sites and to promote bone marrow angiogenesis in nonobese diabetic-severe combined immunodeficient mice, demonstrating its potential effects on tumor progression. ICER represses the majority of 96 target genes upregulated by CREB. It binds CRE promoters and controls gene expression restoring the normal regulation of major cellular pathways. ICER is subjected to degradation through a constitutively active form of the extracellular signal-regulated protein kinase, which drives it to the proteasome. We propose that ICER is downregulated in HL60 to preserve CREB overexpression, which disrupts normal myelopoiesis and promotes blast proliferation. These findings define the function of ICER as a tumor suppressor in leukemia. Unbalanced CREB/ICER expression needs to be considered a pathogenetic feature in leukemogenesis. The molecular characterization of this pathway could be useful for novel therapeutic strategies.
    Subject(s): Hematologic and hematopoietic diseases ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Biological and medical sciences ; Medical sciences ; Neoplasm Transplantation ; Leukemia, Promyelocytic, Acute - pathology ; Jurkat Cells ; Humans ; Extracellular Signal-Regulated MAP Kinases - metabolism ; Gene Expression Regulation, Leukemic ; Cyclic AMP Response Element Modulator - metabolism ; Mice, SCID ; Disease Progression ; Down-Regulation - physiology ; Phenotype ; Animals ; Cyclic AMP Response Element Modulator - genetics ; Leukemia, Promyelocytic, Acute - physiopathology ; Cyclic AMP Response Element-Binding Protein - metabolism ; HL-60 Cells ; Mice, Inbred NOD ; Blast Crisis - genetics ; Mice ; HeLa Cells ; Leukemia, Promyelocytic, Acute - genetics ; Proteasome Endopeptidase Complex - metabolism ; Care and treatment ; Proteolysis ; Leukemia ; Physiological aspects ; Genetic aspects ; DNA binding proteins ; Research ; Gene expression
    ISSN: 0887-6924
    E-ISSN: 1476-5551
    Source: Nature Open Access
    Source: Academic Search Ultimate
    Source: Alma/SFX Local Collection
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 6
    Language: English
    In: Leukemia, 2011, Vol.25 (3), p.560-563
    Subject(s): Hematologic and hematopoietic diseases ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Biological and medical sciences ; Medical sciences ; Translocation, Genetic ; Histone-Lysine N-Methyltransferase ; Genomics ; Humans ; Male ; Gene Expression Profiling ; Chromosomes, Human, Pair 6 ; Myosins - genetics ; Myeloid-Lymphoid Leukemia Protein - genetics ; Kinesin - genetics ; Female ; Chromosomes, Human, Pair 11 ; Child ; Leukemia, Myeloid, Acute - genetics ; Gene expression ; Research
    ISSN: 0887-6924
    E-ISSN: 1476-5551
    Source: Nature Open Access
    Source: Academic Search Ultimate
    Source: Alma/SFX Local Collection
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 7
    Language: English
    In: Leukemia, 2011, Vol.25 (1), p.173-174
    Subject(s): Hematologic and hematopoietic diseases ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Biological and medical sciences ; Medical sciences ; fms-Like Tyrosine Kinase 3 - genetics ; Humans ; Adolescent ; Child, Preschool ; Female ; Infant ; Isocitrate Dehydrogenase - genetics ; Italy ; Male ; Mutation ; Child ; Leukemia, Myeloid, Acute - genetics ; Genetic aspects ; Gene mutations ; Health aspects ; Cancer in children
    ISSN: 0887-6924
    E-ISSN: 1476-5551
    Source: Nature Open Access
    Source: Academic Search Ultimate
    Source: Alma/SFX Local Collection
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 8
    Language: English
    In: Cancer research (Chicago, Ill.), 2009, Vol.69 (6), p.2471-2478
    Description: The cyclic AMP-responsive element binding protein (CREB) is documented to be overexpressed in leukemia, but the underlying mechanism remains unknown. Here, microRNAs (miRNA), which act as negative regulators of gene expression principally through translational repression, are investigated for the mediation of high CREB protein levels. A series of miRNAs that target CREB were identified. Real-time quantitative PCR revealed that miR-34b was expressed significantly less in myeloid cell lines, previously known for high CREB protein levels. Exogenous miR-34b expression was induced, and results revealed a direct interaction with the CREB 3'-untranslated region, with the consequent reduction of the CREB protein levels in vitro. miR-34b restored expression caused cell cycle abnormalities, reduced anchorage-independent growth, and altered CREB target gene expression, suggesting its suppressor potential. Using reverse-phase protein array, CREB target proteins (BCL-2, cyclin A1, cyclin B1, cyclin D, nuclear factor-kappaB, Janus-activated kinase 1, and signal transducer and activator of transcription 3), as well as many downstream protein kinases and cell survival signaling pathways (AKT/mammalian target of rapamycin and extracellular signal-regulated kinase) usually elicited by CREB, were observed to have decreased. The miR-34b/miR-34c promoter was shown to be methylated in the leukemia cell lines used. This epigenetic regulation should control the observed miR-34b expression levels to maintain the CREB protein overexpressed. In addition, the inverse correlation between miR-34b and CREB expression was found in a cohort of 78 pediatric patients at diagnosis of acute myeloid leukemia, supporting this relationship in vivo. Our results identify a direct miR-34b target gene, provide a possible mechanism for CREB overexpression, and provide new information about myeloid transformation and therapeutic strategies.
    Subject(s): Hematologic and hematopoietic diseases ; Pharmacology. Drug treatments ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Biological and medical sciences ; Medical sciences ; Antineoplastic agents ; Tumors ; Promoter Regions, Genetic ; RNA, Small Interfering - genetics ; Acute Disease ; Cyclic AMP Response Element-Binding Protein - biosynthesis ; Gene Expression ; Humans ; Leukemia, Myeloid - genetics ; MicroRNAs - biosynthesis ; Leukemia, Myeloid - pathology ; Cyclic AMP Response Element-Binding Protein - genetics ; DNA Methylation ; Transfection ; Leukemia, Myeloid - metabolism ; Cell Line, Tumor ; HL-60 Cells ; Transcription, Genetic ; MicroRNAs - genetics ; 3' Untranslated Regions ; Cell Growth Processes - genetics
    ISSN: 0008-5472
    E-ISSN: 1538-7445
    Source: HighWire Press (Free Journals)
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 9
    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 ...
  • 10
    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 ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...