title: Loss of B-cell receptor expression defines a subset of diffuse large B-cell lymphoma characterized by silent BCR/PI3K/AKT signaling and a germinal center phenotype displaying low-risk clinicopathologic features.
abstract: B-cell receptor (BCR) signaling is crucial for the survival of normal and neoplastic B cells, and inhibitors targeting BCR signaling pathways have shown promising therapeutic outcomes for patients with B-cell lymphomas. In the current study, we analyzed de novo diffuse large B-cell lymphoma without BCR expression (DLBCL, BCR) in 25 cases to determine the BCR/phosphatidylinositol-3-kinase/AKT (BCR/PI3K/AKT) signaling status, clinicopathologic features, and underlying causes leading to the loss of BCR. On the basis of clinical features, 15 (60%) DLBCL, BCR patients were classified into the low-risk group, and 18 (86%) experienced complete remission. Morphologically and immunophenotypically, DLBCL, BCR demonstrated centroblastic cytology (21/25, 84%) and germinal center B-cell-like cell origin (18/25, 72%). Other components in BCR complexity remained intact, on the basis of immunohistochemical findings. Epstein-Barr virus infection, deficiency in B-lineage transcription factors (PAX5, Oct-2, and Bob.1), and oncogene rearrangement did not seem to be associated with BCR loss. The activated form of signaling proteins (pSYK and pAKT) involved in the BCR/PI3K/AKT pathway were expressed at low levels in DLBCL, BCR tissue. In vitro validation revealed that in DLBCL, BCR cell lines, the BCR/PI3K/AKT pathway did not respond to BCR stimulation or inhibition. Our findings suggest that DLBCL, BCR was characterized by a silent BCR/PI3K/AKT pathway, germinal center phenotype, and low risk and may not be a candidate for BCR-targeted therapies.
authors.affiliation: *Department of Pathology, Fudan University Shanghai Cancer Center †Department of Oncology, Shanghai Medical College §Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai ‡Department of Pathology, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, P.R. China.
authors.forename: Wei-Ge
authors.initials: WG
authors.lastname: Wang
authors.forename: Wen-Li
authors.initials: WL
authors.lastname: Cui
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Fen
authors.initials: F
authors.lastname: Zhu
authors.forename: Xiao-Chun
authors.initials: XC
authors.lastname: Wan
authors.forename: Bo
authors.initials: B
authors.lastname: Ping
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; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018858:Germinal Center; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000145:classification* / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D051058:Oncogene Protein v-akt / Q000502:physiology*; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D051562:Proto-Oncogene Proteins c-bcr / Q000502:physiology*; D018570:Risk Assessment; D015398:Signal Transduction; D055815:Young Adult
chemical_list: D019869:Phosphatidylinositol 3-Kinases; C496613:BCR protein, human; D051058:Oncogene Protein v-akt; D051562:Proto-Oncogene Proteins c-bcr