Focal Rosai-Dorfman disease coexisting with lymphoma in the same anatomic site: a localized histiocytic proliferation associated with MAPK/ERK pathway activation.
Nevertheless, the expression of p-ERK in three cases suggests that the RAS-RAF-MAP2K-ERK pathway is activated, perhaps by non-mutational mechanisms induced by the presence of lymphoma or lymphoma-microenvironment interactions.
Mechanistically, SHP2/ERK inhibition impedes c-Myc transcriptional activity, which results in the repression of proliferative phenotype signatures of germinal center lymphoma.
Overexpression of GPR34 in lymphoma and HeLa cells resulted in phosphorylation of ERK, PKC, and CREB; induced CRE, AP1, and NF-κB-mediated gene transcription; and increased cell proliferation.
Combined, these results implicate epigenetic silencing of Spry2 expression in B lymphoma progression and suggest it as a companion lesion to ectopic TCL1 expression in enhancing MAPK-ERK pathway signaling.