Diffuse large B-cell lymphoma with low ¹⁸F-fluorodeoxyglucose avidity features silent B-cell receptor signaling

Abstract

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of aggressive lymphomas exhibiting increased glucose uptake. However, some DLBCLs featuring relatively low ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) uptake denoted by the maximum standardized uptake value (SUV_max) on PET/CT have been identified. The biologic correlates of such a heterogeneity have remained largely unknown. Herein, we immunohistochemically detected and found low FDG-avid DLBCL cases featuring lower expression of some key molecules involved in B-cell receptor (BCR) signaling (pSYK) and glucose metabolism (GLUT1 and HK2). Besides, BCR-deficient DLBCL xenografts were found displaying lower SUV_max and expressions of pSYK, GLUT1, and HK2. Further immunoblotting demonstrated expressions of GLUT1 and HK2 in BCR-dependent DLBCLs could be down-regulated by a chemical SYK inhibition, whereas the inhibitory effects were not observed in BCR-deficient tumors. These findings suggest low FDG-avid DLBCLs display a silent BCR signaling and PET/CT might be utilized to tailor the BCR signaling-inhibitory treatment.

Keywords:

• Diffuse large B-cell lymphoma
• PET/CT
• B-cell receptor signaling
• pSYK
• GLUT1
• HK2

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by a grant from the Guide Project of Science and Technology Commission of Shanghai Municipality [134119a5000] and a grant from the Natural Science Foundation of Shanghai Municipality [11ZR1407100].