PDE4D and diffuse large B-cell lymphoma: Activation of BCR/TCR was suggested by upregulation of CARD11, CLECL1 (encoding a T-cell costimulatory molecule), and IGHM. However, inhibition of BCR/TCR and increased threshold for activation in CD5+ DLBCL was also suggested by upregulation of PTPN2 and SIT1 (which negatively regulate TCR signaling), LYN (which has roles in inhibiting BCR), and SH3BP5 (which inhibits BTK signaling), and downregulation of PDE4D (which hydrolyzes c-AMP, thereby removing the c-AMP constraint for TCR) in CD5+ DLBCL [43].