Unknown,Transcriptomics,Genomics,Proteomics

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Direct in vivo evidence for B-cell receptor and NF-KB activation in mantle cell lymphoma: role of the lymph node microenvironment and activating mutations. [RNA-Seq]


ABSTRACT: We provide direct in vivo evidence for activation of the BCR and canonical NF-KB pathways in MCL that, in the absence of activating mutations, is dependent on the lymph node microenvironment. This finding provides a mechanistic explanation for the surprising efficacy of ibrutinib for the treatment of this type of lymphoma. Mutations in components of the BCR and NF-KB pathways are associated with cell-autonomous signaling and resistance to ibrutinib. Lymph node biopsies and peripheral blood samples were obtained from patients with previously untreated MCL.

ORGANISM(S): Homo sapiens

SUBMITTER: Delong Liu 

PROVIDER: E-GEOD-70926 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications


To interrogate signaling pathways activated in mantle cell lymphoma (MCL) in vivo, we contrasted gene expression profiles of 55 tumor samples isolated from blood and lymph nodes from 43 previously untreated patients with active disease. In addition to lymph nodes, MCL often involves blood, bone marrow, and spleen and is incurable for most patients. Recently, the Bruton tyrosine kinase (BTK) inhibitor ibrutinib demonstrated important clinical activity in MCL. However, the role of specific signali  ...[more]

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