Jun-regulated genes promote interaction of diffuse large B-cell lymphoma with the microenvironment

Blonska, Marzenna; Zhu, Yifan; Chuang, Hubert H.; You, M. James; Kunkalla, Kranthi; Vega, Francisco; Lin, Xin

doi:10.1182/blood-2014-04-568188

Cited by 58 publications

(53 citation statements)

References 48 publications

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“…In this regard, the function of SH3BP5 resembles that of ibrutinib, a BTK inhibitor that is highlighted for its remarkable antitumor effect in B‐cell malignancies 17, 18. SH3BP5 also interacts with c‐Jun NH2‐terminal kinase (JNK) 19, which is required for survival and proliferation of B‐cell lymphoma cells 20, 21. The endogenous level of SH3BP5 positively regulates JNK 22, 23; however, the overexpressed SH3BP5 inhibits JNK 24.…”

Section: Discussionmentioning

confidence: 99%

Expressions of SH3BP5, LMO3, and SNAP25 in diffuse large B‐cell lymphoma cells and their association with clinical features

et al. 2016

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Diffuse large B‐cell lymphoma (DLBCL) is clinicopathologically and genetically heterogeneous with variable clinical outcomes. We previously identified signature genes overexpressed in CD5‐positive (CD5+) DLBCL, which is a poor prognostic subgroup of DLBCL. To elucidate the clinical significance of the protein expression of the signature genes overexpressed in CD5+ DLBCL with regard to all DLBCL, not otherwise specified (NOS), 10 genes (SH3BP5,LMO3,SNAP25,SYT5,SV2C,CABP1,FGF1,FGFR2,NEUROD1, and SYN2) were selected and examined immunohistochemically with samples from 28 patients with DLBCL, NOS. Only three protein expressions, SH3BP5, LMO3, and SNAP25, were detected in DLBCL cells and then analyzed further with samples from 187 patients with DLBCL, NOS. The SH3BP5, LMO3, and SNAP25 proteins were expressed in 60% (103/173), 34% (59/175), and 46% (77/168) of DLBCL patients, respectively. These protein expressions were associated with CD5 expression, and only SH3BP5 was frequently expressed in activated B‐cell‐like DLBCL (P = 0.046). Compared to the SH3BP5‐negative group, the SH3BP5+ group was correlated with elderly onset (>60 years, P = 0.0096) and advanced‐stage disease (stage III/IV, P = 0.037). The LMO3+ group showed a worse performance status (>1, P = 0.0004). The SH3BP5+ group and the LMO3+ group had significantly worse overall survival than the negative groups (P = 0.030, 0.034; respectively) for the entire group. In a subgroup analysis of patients treated with rituximab‐containing chemotherapy, there was no significant difference between groups. To the best of our knowledge, this is the first report showing the protein expressions of SH3BP5, LMO3, and SNAP25 in DLBCL cells and their clinical significance in patients with DLBCL. The SH3BP5 and LMO3 protein expressions are associated with the baseline clinical characteristics of DLBCL.

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Section: Discussionmentioning

confidence: 99%

Expressions of SH3BP5, LMO3, and SNAP25 in diffuse large B‐cell lymphoma cells and their association with clinical features

et al. 2016

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“…Increased serum levels of bFGF have been reported in CLL, and plasma cell myeloma and expression of bFGF was found in tumor cells in CLL/SLL, FL, DLBCL, MCL, Burkitt and lymphoblastic lymphomas [55]. Interestingly, our recent study revealed that the direct interaction of DLBCL cells with mesenchymal cells strongly enhanced the production of bFGF and VEGF by lymphoma cells [56].…”

Section: Vessels and Endothelial Cellsmentioning

confidence: 93%

Shaping of the tumor microenvironment: Stromal cells and vessels

Blonska

Agarwal

Vega

2015

Seminars in Cancer Biology

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Lymphomas develop and progress in a specialized tissue microenvironment such as bone marrow as well as secondary lymphoid organs such as lymph node and spleen. The lymphoma microenvironment is characterized by a heterogeneous population of stromal cells, including fibroblastic reticular cells, nurse-like cells, mesenchymal stem cells, follicular dendritic cells, and inflammatory cells such as macrophages, T- and B-cells. These cell populations interact with the lymphoma cells to promote lymphoma growth, survival and drug resistance through multiple mechanisms. Angiogenesis is also recognized as an important factor associated with lymphoma progression. In recent years, we have learned that the interaction between the malignant and non-malignant cells is bidirectional and resembles, at least in part, the pattern seen between non-neoplastic lymphoid cells and the normal microenvironment of lymphoid organs. A summary of the current knowledge of lymphoma microenvironment focusing on the cellular components will be reviewed here.

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“…Consequently, the residual low levels of p-JNK observed after treatment with HG6-64-1 may lead to a better therapeutic window compared with direct JNK inhibitors. However, Jun-regulated genes activation was recently reported to promote lymphoma growth and dissemination to extranodal sites in DLBCL, 41 and the JNK pathway was reported as a therapeutic target in ABC-like DLBCL 42 ; so it is possible that direct JNK inhibition should be revisited in future studies.…”

Section: Discussionmentioning

confidence: 99%

Pathophysiological significance and therapeutic targeting of germinal center kinase in diffuse large B-cell lymphoma

Matthews

Bhatt

Patricelli³

et al. 2016

Blood

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Jun-regulated genes promote interaction of diffuse large B-cell lymphoma with the microenvironment

Abstract: Key Points Elevated Jun signaling promotes lymphoma growth and dissemination to extranodal sites. Jun-regulated genes mediate the interaction of malignant cells with stromal cells and adhesion to extracellular matrix proteins.

Cited by 58 publications

References 48 publications

Expressions of SH3BP5, LMO3, and SNAP25 in diffuse large B‐cell lymphoma cells and their association with clinical features

Expressions of SH3BP5, LMO3, and SNAP25 in diffuse large B‐cell lymphoma cells and their association with clinical features

Shaping of the tumor microenvironment: Stromal cells and vessels

Pathophysiological significance and therapeutic targeting of germinal center kinase in diffuse large B-cell lymphoma

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