Genomewide gene expression analysis of lymphoid cell lines of Hodgkin, non-Hodgkin and acute leukemia origin
High-level expression of Mastermind-like 2 contributes to aberrant activation of the NOTCH signaling pathway in human lymphomas.
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View SamplesCutaneous T-cell lymphomas form a heterogeneous group of non-Hodgkin lymphomas characterized by only poor prognosis in advanced stage. Despite significant progress made in the identification of novel genes and pathways involved in the pathogenesis of cutaneous lymphoma, the therapeutic value of these findings has still to be proven. Here, we demonstrate by gene expression arrays that aurora kinase A is one of highly overexpressed genes of the serine/threonine kinase in CTCL. The finding was confirmed by qualitative RT-PCR, Western blotting and immunohistochemistry in CTCL cell lines and primary patient samples. Moreover, treatment with a specific aurora kinase A inhibitor blocks cell proliferation by inducing cell cycle arrest in G2 phase as well as apoptosis in CTCL cell lines. These new data provide a promising rationale for using aurora kinase A inhibition as a therapeutic modality of CTCL.
Aurora Kinase A Is Upregulated in Cutaneous T-Cell Lymphoma and Represents a Potential Therapeutic Target.
Specimen part, Subject
View SamplesThe aim of the study was to get insights into transcriptional alterations in bone marrow mesenchymal stromal cells derived from acute myeloid leukemia patients
Molecular alterations in bone marrow mesenchymal stromal cells derived from acute myeloid leukemia patients.
Disease
View SamplesIn human chronic lymphocytic leukemia (CLL) pathogenesis B cell antigen receptor signaling seems important for leukemia B cell ontogeny, whereas the microenvironment influences B cell activation, tumor cell lodging and provision of antigenic stimuli. Using the murine E-Tcl1 CLL model, we demonstrate that CXCR5-controlled access to follicular dendritic cells (FDCs) confers proliferative stimuli to leukemia B cells. Intravital imaging revealed a marginal zone B cell-like leukemia cell trafficking route. Murine and human CLL cells reciprocally stimulated resident mesenchymal stromal cells through lymphotoxin--receptor activation, resulting in CXCL13 secretion and stromal compartment remodeling. Inhibition of lymphotoxin/lymphotoxin--receptor signaling or of CXCR5 signaling retards leukemia progression. Thus, CXCR5 activity links tumor cell homing, shaping a survival niche, and access to localized proliferation stimuli.
Access to follicular dendritic cells is a pivotal step in murine chronic lymphocytic leukemia B-cell activation and proliferation.
Specimen part
View SamplesThree ALCL cell lines DEL, FEPD and K299 were induced with an IRF4-specific shRNA for up to 96 hours.
Essential role of IRF4 and MYC signaling for survival of anaplastic large cell lymphoma.
Cell line
View SamplesGenome-wide gene expression analysis of Reh cells following transfection with constitutively active IRF5-4D, constitutively active IKK(EE), or both in combination.
Mapping of transcription factor motifs in active chromatin identifies IRF5 as key regulator in classical Hodgkin lymphoma.
Cell line
View SamplesGenome-wide gene expression analysis of Reh cells following transfection with shRNA targeting CBFA2T3, constitutively active IKK(EE), or both in combination.
Derepression of an endogenous long terminal repeat activates the CSF1R proto-oncogene in human lymphoma.
Cell line
View SamplesGenome-wide gene expression analysis of murine splenic B-cells following retroviral transduction with a constitutively active IRF5 (IRF5-4D)
Mapping of transcription factor motifs in active chromatin identifies IRF5 as key regulator in classical Hodgkin lymphoma.
Specimen part
View SamplesMantle cell lymphoma (MCL) is a mature B-cell lymphoma characterized by poor clinical outcome. Recent studies revealed the importance of BCR signaling in maintaining MCL survival. However, it remains unclear which role MALT1, an essential component of the CARD11-BCL10-MALT1 (CBM) complex that transfers BCR signaling to the NF-kB pathway, plays in the biology of MCL. Here we show that a subset of MCLs is addicted to MALT1, as its inhibition by either RNA or pharmacologic interference induced cytotoxicity both in vitro and in vivo. Gene expression profiling following MALT1 inhibition demonstrated that MALT1 controls a MYC-driven gene expression network predominantly through increased MYC protein stability. Thus our analyses identify a previously unappreciated regulatory mechanism of MYC expression. Investigating primary mouse splenocytes, we could demonstrate that MALT1 induced MYC regulation is not restricted to MCL, but represents a common mechanism of MYC regulation. MYC itself is pivotal for MCL survival as its downregulation and pharmacologic inhibition induced cytotoxicity in all MCL models. Collectively, these results provide a strong mechanistic rationale to investigate the therapeutic efficacy in targeting the MALT1-MYC axis in MCL patients.
B-cell receptor-driven MALT1 activity regulates MYC signaling in mantle cell lymphoma.
Specimen part, Cell line
View SamplesA growing number of studies on gynecological cancers (GCs) have revealed potential gene markers associated either with the pathogenesis and progression of the disease on representing putative targets for therapy and treatment of cervical (CC), endometrial (EC) and vulvar cancer (VC). However, quite a little overlap is found between these data. In this study we combined data from the three GCs integrating gene expression profile analysis.
Profiling of Discrete Gynecological Cancers Reveals Novel Transcriptional Modules and Common Features Shared by Other Cancer Types and Embryonic Stem Cells.
Specimen part, Disease, Disease stage
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