Indolent MCL identified by genomic and gene expression profiling
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE16455 | GEO | 2010/03/04
SECONDARY ACCESSION(S): PRJNA116025
REPOSITORIES: GEO
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Project description:Mantle cell lymphoma (MCL) is an aggressive neoplasm with poor outcome. However, some patients have an indolent disease (iMCL) and may not require intensive treatment at initial diagnosis. Diagnostic criteria to recognize these patients are not available. We hypothesized that the analysis of the genetic and expression features of the tumors may help to identify patients with an indolent clinical evolution and provide biomarkers that could be used in the clinical setting. Seven patients with an iMCL that did not require chemotherapy for more than 2 years were compared to 15 conventional MCL (cMCL) that needed systemic therapy at diagnosis. MCL were compared with other leukemic lymphoid neoplasms including 17 CLL, 7FL, HCL and 2HCLv.
2010-03-04 | E-GEOD-16455 | biostudies-arrayexpress
Project description:Mantle cell lymphoma (MCL) is an aggressive B-cell neoplasm characterized by the t(11;14)(q13;q32) translocation leading to cyclin D1 overexpression. Cyclin D1 is a major cell cycle regulator and also has a role in transcription, but the effect of the latter in tumorigenesis remains largely unknown. Here, we investigated the transcriptional role of cyclin D1 in MCL and its impact on the pathogenesis of this neoplasm. Integrating genome-wide expression analysis of cyclin D1-silenced and overexpressing cells with cyclin D1 chromatin binding profiles, we identified a cyclin D1-activated transcriptional program in MCL cells.
2021-06-30 | GSE144106 | GEO
Project description:The aggressive clinical behavior of mantle cell lymphoma (MCL) is attributed to specific genetic and molecular mechanisms involved in its pathogenesis, mainly the t(11;14)(q13;q32) traslocation and cyclin D1 (CCND1) overexpression. Nevertheless, evidence of a certain degree of clinical/biological heterogeneity has been disclosed by gene expression profile (GEP) and (immuno)genetic/immunohistochemistry studies. AIM: To use a GEP approach to identify MCL subsets with peculiar clinical/biological features in the context of of MCL patients treated homogeneously with an autologous transplantation-based program.
2017-12-31 | GSE89447 | GEO
Project description:Patients with conventional mantle cell lymphoma (MCL) show an aggressive clinical behavior. However, cases fulfilling the WHO criteria for MCL, but that remain asymptomatic without treatment, have been reported. In an attempt to understand this heterogeneity, we have compared 17 typical cases of MCL with a homogeneous group of 13 asymptomatic individuals with monoclonal expansion of t(11;14)(q13;q32) cyclin D1-positive B-cells in peripheral blood (MALD1). None of these cases have received treatment (minimum follow-up of 26 months; median, 71 months). Gene expression analysis has shown enrichment of signatures associated to neoplastic behavior and cell proliferation in MCL but not in MALD1. In contrast, MALD1 was highly enriched in gene sets related to immune activation and inflammatory responses. CD38 and CD200 genes were differentially expressed between MCL and MALD1. The combined assessment of both proteins by flow cytometry allowed classifying 85% of MALD1 cases. In summary, we have shown for the first time that MALD1, in contrast to MCL, is characterized by immune activation and driven by inflammatory cues. We have also shown that CD38 and CD200 flow cytometry assessment is useful to discern most cases of MALD1 from MCL in the clinical setting. MALD1 should be identified and segregated from the current MCL category to avoid overdiagnosis and unnecessary treatment. 18 samples were analyzed: 5 MALD1, 5 MCL and 8 Healthy Controls
2013-12-23 | E-GEOD-45717 | biostudies-arrayexpress
Project description:Patients with conventional mantle cell lymphoma (MCL) show an aggressive clinical behavior. However, cases fulfilling the WHO criteria for MCL, but that remain asymptomatic without treatment, have been reported. In an attempt to understand this heterogeneity, we have compared 17 typical cases of MCL with a homogeneous group of 13 asymptomatic individuals with monoclonal expansion of t(11;14)(q13;q32) cyclin D1-positive B-cells in peripheral blood (MALD1). None of these cases have received treatment (minimum follow-up of 26 months; median, 71 months). Gene expression analysis has shown enrichment of signatures associated to neoplastic behavior and cell proliferation in MCL but not in MALD1. In contrast, MALD1 was highly enriched in gene sets related to immune activation and inflammatory responses. CD38 and CD200 genes were differentially expressed between MCL and MALD1. The combined assessment of both proteins by flow cytometry allowed classifying 85% of MALD1 cases. In summary, we have shown for the first time that MALD1, in contrast to MCL, is characterized by immune activation and driven by inflammatory cues. We have also shown that CD38 and CD200 flow cytometry assessment is useful to discern most cases of MALD1 from MCL in the clinical setting. MALD1 should be identified and segregated from the current MCL category to avoid overdiagnosis and unnecessary treatment.
2013-12-23 | GSE45717 | GEO
Project description:The aggressive clinical behavior of mantle cell lymphoma (MCL) is attributed to specific genetic and molecular mechanisms involved in its pathogenesis, mainly the t(11;14)(q13;q32) traslocation and cyclin D1 (CCND1) overexpression. Nevertheless, evidence of a certain degree of heterogeneity has been disclosed by gene expression profile (GEP) and (immuno)genetic/immunohistochemistry studies. AIM: To use a GEP approach in MCL cell line models.
2017-12-31 | GSE89615 | GEO
Project description:Phosphatidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway activation contributes to mantle cell lymphoma (MCL) pathogenesis and drug resistance. However, the use of mTOR inhibitors as single agents have shown limited clinical efficacy in relation with drug activation of feedback loops. Selective PI3K inhibition or dual PI3K/mTOR catalytic inhibition are different therapeutic approaches developed to achieve effective pathway blockage. Here, we evaluated the antitumor activity of a mTOR inhibitor, a pan-PI3K inhibitor and a dual PI3K/mTOR inhibitor in primary MCL cells. We found that dual PI3K/mTOR inhibitor modulated angiogenesis, tumor invasiveness and cytokine signaling compared to a mTOR inhibitor and a pan-PI3K inhibitor in MCL. We used microarrays to compare the effect of these three compounds in MCL and identified distinct classes of down-regulated genes modulated by each compound. Global RNA expression in primary cells from two MCL patients treated with a mTOR inhibitor, a pan-PI3K inhibitor and a dual PI3K/mTOR inhibitor for 8 hours
2013-12-14 | E-GEOD-53309 | biostudies-arrayexpress
Project description:The purpose of this registry is to obtain a general view as regards efficacy, tolerability and safety issues of the Torisel, Sutent, and/or Inlyta therapies in patients with advanced renal cell carcinoma, recurrent / refractory mantle cell lymphoma (MCL) and gastro-intestinal stroma tumors (GIST) under the conditions of routine use
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Project description:Mantle cell lymphoma (MCL) is a rare, highly heterogeneous type of B-cell non-Hodgkin’s lymphoma (NHL) driven by multiple genetic mutations disrupting cell cycle regulation and DNA damage response. Despite advances in therapy, novel treatment approaches are needed especially for highly proliferative MCL which has a particularly progressive clinical course even in the era of Bruton’s tyrosine kinase therapy. The sumoylation pathway is known to be upregulated in many cancers including lymphoid malignancies. However, little is currently known about the role of the sumoylation pathway and its oncogenic potential in MCL. We found extensive upregulation of the sumoylation pathway in MCL, particularly at the level of the E1 enzymes SAE1 and SAE2, with elevated expression levels of sumoylation enzyme components showing a worse prognosis and a strong positive correlation with cell cycle associated genes. Targeting the sumoylation pathway with TAK-981, a first in class sumoylation inhibitor currently being investigated in a clinical study of B-cell NHL in combination with rituximab (NCT04074330), resulted in potent loss of sumoylation in MCL cells with significant activity in in-vitro and in vivo models of MCL, including ibrutinib resistance cases. We found mitotic dysregulation to be an important, although not all encompassing mechanism of cell death upon loss of sumoylation of TAK-981 in MCL cells. We uncovered a diverse sumoylation program upon mitosis entry that was significantly reduced with TAK-981. Centromeric localization of the well known sumoylation substrate topoisomeraseIIA (TopIIA) was significantly abrogated upon mitosis entry, likely contributing at least in part to the mitotic dysregulation seen in MCL cells. This mechanism is highly relevant as TopIIA is significantly upregulated in MCL with SAE1/2 overexpression. Our study, in addition to the recently described immunomodulatory activity of TAK-981, not only validates SAE1/2 as a therapeutic target in MCL but also opens the door to further mechanistic work to uncover how to best use desumoylation therapy to treat MCL and other lymphoid malignancies.
2022-09-02 | GSE184031 | GEO
Project description:We provide RNA sequencing data for a Ccnd2/p53/Mb1Cre mouse model (Mb1Cre is active from pre-B cells onwards). This mouse model features Ccnd2 overexpression and p53 loss in B-cells, and develops tumors that resembles Mantle cell lymphoma (MCL). These Ccnd2/p53/Mb1Cre mice develop both non-MCL and MCL-like lymphomas and RNA samples from both groups were sequenced. Fresh lymphoma cells (5x10exp6) were frozen in 700 µl of QIAZOL and stored in -80°C. RNA was prepared using a miRNeasy mini kit (Qiagen).
2021-08-10 | GSE175568 | GEO