In this study, we analyzed the prevalence of 9p24.1 CNA in newly diagnosed DLBCL and examined its association with PD-L1, PD-L2, and JAK2 expression, clinical characteristics, and outcome.
We found that PD-L1 expression, particularly in nongerminal center B cell-derived diffuse large B-cell lymphoma (DLBCL), is controlled and regulated by several interactive signaling pathways, including the B-cell receptor (BCR) and JAK2/STAT3 signaling pathways.
The place of JAK2 inhibitors in the treatment of diffuse large B-cell lymphoma has not been defined; we suggest that JAK2 inhibitors might be most effective in poor prognosis ABC-DLBCL, which shows higher levels of IL10RA, JAK2, and STAT3 but lower levels of BCL6 than GC-DLBCL and might be usefully combined with novel approaches such as inhibition of IL10RA.
HDAC inhibition abolished STAT3(Tyr705) phosphorylation with minimal effect on STAT3(Ser727) and JAK2 tyrosine activity. pSTAT3(Tyr705)-positive DLBCLs were more sensitive to HDAC inhibition with LBH589 compared with pSTAT3(Tyr705)-negative DLBCLs.
Recently, our work comparing gene expression signatures of primary mediastinal large B-cell lymphomas (PMLBCL) versus nodal diffuse large B-cell lymphomas revealed a relative increase in JAK2 transcripts in the former, suggesting a role for increased JAK2 signaling in a subset of these tumors.
Fluorescence in situ hybridization analysis did not reveal involvement of the JAK2 gene, located at chromosome band 9p24, and previously shown to be amplified in Hodgkin lymphoma and primary mediastinal diffuse large B-cell lymphoma.