Fig. 2

Oncogenic (deregulated) intracellular signaling pathways in germinal center B cell-like (GCB) diffuse large B-cell lymphoma (DLBCL). Germinal center B cell-like diffuse large B-cell lymphoma (GCB-DLBCL) are characterized by the inactivation or loss of the phosphatase and tensin homologue (PTEN) and S1PR2-Gα13-ARHGEF1 signaling pathways, which both negatively modulate GC B cell migration and phosphatidylinositol-3-kinase (PI3K) signaling [13, 82–84, 324, 593]. In addition, activating mutations of the histone methyltransferase EZH2 (enhancer of zeste homologue 2) and master regulator of the GCB phenotype promote epigenetic changes that, at least partly, cooperate with the B-cell lymphoma 2 (BCL2) and BCL6 to mediate lymphomagenesis in GCB-DLBCL [77, 79]. A subset of GCB-DLBCL is characterized by translocations affecting the c-MYC and/or the BCL2 loci [80, 81, 87]. These translocations lead to constitutive activation of c-MYC and the anti-apoptotic BCL2 protein and to a malignant transformation by preventing terminal differentiation or blocking apoptosis. The different colors that are used in the figure indicate molecules that belong to a specific pathway and/or lead to a specific outcome. Adapted from REF: [3, 70, 86, 109]. Information for this figure was gleaned from the following references: [2, 3, 13, 15–18, 20, 29, 39, 66, 75–84, 86, 87, 93, 109, 123, 148, 247–251, 259, 324, 325, 352, 354–356, 360–365, 367, 374, 375, 377, 380–382, 384–386, 593, 612]. Abbreviations: S1PR2 sphingosine-1-phosphate receptor-2, Gα13 (GNA13) heterotrimeric G protein alpha 13, ARHGEF1 Rho guanine nucleotide exchange factor (GEF) 1, PI3K phosphoinositide 3-kinase, mTORC1 mammalian target of rapamycin (mTOR) complex 1, BCL6 B cell lymphoma protein 6, BCL2 B cell lymphoma protein 2, EZH2 enhancer of zeste homologue 2