title: MYC Protein-positive Diffuse Large B-Cell Lymphoma Features an Activated B-Cell Receptor Signal Pathway.
abstract: Components of the B-cell receptor (BCR) signaling pathway represent promising therapeutic targets in diffuse large B-cell lymphoma (DLBCL) and other B-cell malignancies. MYC, a transcriptional factor and oncoprotein, is overexpressed in a fraction of DLBCL and indicates poor prognosis and aggressive clinical course when treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). However, BCR signaling status in MYC-positive DLBCL cases and the potential efficacy of BCR signal inhibitors in treating this aggressive disease are unknown. To further elucidate the BCR signaling pathway in MYC-positive DLBCL, we analyzed the levels of BCR-associated genes according to MYC gene status, detected phosphorylated protein with primary DLBCL samples, and estimated the patient survival with MYC expression. In addition, we manipulated MYC gene expression and tested its effects on BCR signaling in vitro. We found that CD19, SYK, and BLK were highly expressed in DLBCL with MYC gene overexpression. MYC-positive DLBCL had higher levels of pSYK and pBLK, but only pSYK level correlated with patient survival. The in vitro studies demonstrated that overexpression of the MYC gene augmented BCR signaling, whereas MYC gene knockdown attenuated BCR signaling. Thus, MYC protein-positive DLBCL features highly activated BCR signaling and may represent a potential candidate for BCR inhibitor therapy.
authors.affiliation: *Department of Pathology, Fudan University Shanghai Cancer Center †Department of Oncology, Shanghai Medical College ‡Institute of Pathology, Fudan University, Shanghai, P. R. China.
authors.forename: Wei-Ge
authors.initials: WG
authors.lastname: Wang
authors.forename: Xiang-Nan
authors.initials: XN
authors.lastname: Jiang
authors.forename: Ze-Bing
authors.initials: ZB
authors.lastname: Liu
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Zhou
authors.forename: Xiao-Qiu
authors.initials: XQ
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018941:Antigens, CD19 / Q000235:genetics / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D053208:Kaplan-Meier Estimate; D008213:Lymphocyte Activation; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D034622:RNA Interference; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000378:metabolism*; D012307:Risk Factors; D015398:Signal Transduction; D000072377:Syk Kinase / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D055815:Young Adult; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D018941:Antigens, CD19; D014408:Biomarkers, Tumor; C000604811:CD19 molecule, human; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D011947:Receptors, Antigen, B-Cell; C584409:BLK protein, human; C000606896:SYK protein, human; D000072377:Syk Kinase; D019061:src-Family Kinases