title: Diffuse large B-cell lymphoma with concurrent high MYC and BCL2 expression shows evidence of active B-cell receptor signaling by quantitative immunofluorescence.
abstract: B-cell receptor (BCR)-mediated signaling plays an important role in the pathogenesis of a subset of diffuse large B-cell lymphoma (DLBCL), and novel agents targeting this pathway are now in clinical use. We have previously identified a signature of active BCR signaling on formalin-fixed paraffin-embedded specimens using quantitative immunofluorescence, allowing for identification of patients who might benefit from anti-BCR therapies. We sought to characterize the clinicopathologic significance of active BCR signaling in DLBCL by correlating measures of signaling intensity with clinical features and various tumor cell characteristics. High MYC and concurrent high MYC and BCL2 double-expression was positively correlated with individual markers of active BCR signaling and cases with MYC/BCL2 double-expression showed overall greater BCR activation compared to cases lacking double-expression. Our findings suggest that the BCR signaling pathway may be more active in MYC/BCL2 double-expressor DLBCL and may represent a rational therapeutic target in this aggressive DLBCL subgroup.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Agata M
authors.identifier: http://orcid.org/0000-0003-4332-3582
authors.initials: AM
authors.lastname: Bogusz
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
authors.forename: Alexandra E
authors.initials: AE
authors.lastname: Kovach
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors.forename: Long P
authors.initials: LP
authors.lastname: Le
authors.affiliation: Department of Statistics, Yale University, New Haven, Connecticut, United States of America.
authors.forename: Derek
authors.initials: D
authors.lastname: Feng
authors.affiliation: Department of Chemistry, Yale University, New Haven, Connecticut, United States of America.|Department of Molecular Biophysics & Biochemistry, Yale University, New Haven, Connecticut, United States of America.
authors.forename: Richard H G
authors.initials: RH
authors.lastname: Baxter
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors.forename: Aliyah R
authors.initials: AR
authors.lastname: Sohani
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C000595707:BCL2 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc