Original ArticlesMYC Protein–positive Diffuse Large B-Cell Lymphoma Features an Activated B-Cell Receptor Signal PathwayWang, Wei-Ge MD; Jiang, Xiang-Nan MD; Liu, Ze-Bing MD, PhD; Zhou, Xiao-Yan MD, PhD; Li, Xiao-Qiu MD, PhDAuthor Information *Department of Pathology, Fudan University Shanghai Cancer Center †Department of Oncology, Shanghai Medical College ‡Institute of Pathology, Fudan University, Shanghai, P. R. China W.-G.W. and X.-N.J. contributed equally. Supported by a grant from the Guide Project of Science and Technology Commission of Shanghai Municipality (No. 134119a5000) and the National Natural Science Foundation of China (81272630). Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Xiao-Qiu Li, MD, PhD, Department of Pathology, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai 200032, P. R. China (e-mail: email@example.com). The American Journal of Surgical Pathology: April 2017 - Volume 41 - Issue 4 - p 541-549 doi: 10.1097/PAS.0000000000000799 Buy SDC Metrics 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. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.