CD99 is a 32-kDa transmembrane glycoprotein that is encoded by the MIC2 gene. 
Our study was carried out to examine the role of CD99 in tumor progression of 
classical Hodgkin lymphoma (cHL). Here, we showed that lowly expressed CD99 
protein in cHL cell lines and primary cHL cases correlates with the deficient 
expression of the positive regulatory domain 1 (PRDM1/BLIMP1). In addition, cHL 
cell lines showed high levels of miR-9 expression. We determined that the 
upregulation of CD99 induced expression of transcription factor PRDM1, a master 
regulator of plasma-cell differentiation, which is also a target for 
miR-9-mediated downregulation. Indeed, inhibition of miR-9 also triggered 
upregulation of PRDM1 expression. Furthermore, overexpression of CD99 resulted 
in changed growth features and reorganization of actin cytoskeleton. As 
upregulation of CD99 led to a decrease in cHL diagnosis marker CD30 and CD15 and 
an increase in plasma-cell differentiation marker CD38 and the restoration of 
B-cell makers PAX5, CD79α and CD19, we suggest that downregulated CD99 leads to 
the prevention of plasma-cell differentiation in Hodgkin/Reed-Sternberg (H/RS) 
cells. Furthermore, these data indicate that CD99 may control miR-9 expression, 
which directly targets PRDM1. Altogether, these results reveal a 
CD99-miR-9-PRDM1 molecule axis in lymphomagenesis of cHL and suggest that 
upregulation of CD99 in H/RS cells induces terminal B-cell differentiation, 
which may provide a novel therapeutic strategies for cHL.