Pyruvate dehydrogenase kinase 4-mediated metabolic reprogramming is involved in rituximab resistance in diffuse large B-cell lymphoma by affecting the expression of MS4A1/CD20.

ABSTRACT: Diffuse large B cell lymphoma (DLBCL) heterogeneity promotes recurrence and anti-CD20-based therapeutic resistance. Previous studies have shown that downregulation of MS4A1/CD20 expression after chemoimmunotherapy with rituximab leads to rituximab resistance. However, the mechanisms of CD20 loss remain unknown. We identified that pyruvate dehydrogenase kinase 4 (PDK4) is markedly elevated in DLBCL cells derived from both patients and cell lines with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) resistance. We found that overexpression of PDK4 in DLBCL cells resulted in cell proliferation and resistance to rituximab in vitro and in vivo. Furthermore, loss of PDK4 expression or treatment with the PDK4 inhibitor dichloroacetate was able to significantly in

SUBMITTER: Jiang D 

PROVIDER: S-EPMC8409406 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature