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. 2021 Sep 6;28(5):3430–3447. doi: 10.3390/curroncol28050297

Figure 4.

Figure 4

The top of the figure illustrates the two firsts pathways arising from a naïve B-cell and characterized by a deletion of the long arm of chromosome 7. Pathway n°1 is supposed not to pass through the germinal center. SMZL developed from this pathway presents a repertory bias with a preferential use of IGHV1-2*04 and is supposed not to undergo somatic hypermutation. Pathway n°2 is supposed to pass through the germinal center where somatic hypermutation happens, and mutations involving the non-canonical NFκB pathway and NOTCH1/2 are added (sometimes associated with KLF2 mutations). The third pathway is characterized by mutations of DNA repair genes (TP53) or TLRs genes (MYD88). More studies are required to precisely define these pathways and correlate them with histological patterns, immunohistochemistry, and clinical data (particularly prognosis). Created with BioRender.com. Abbreviations: BIRC3, baculoviral IAP repeat-containing protein 3; IGVH, immunoglobulin G heavy chain; KLF2, Krüppel-like factor 2; MYD88, myeloid differentiation primary response 88; NOTCH, neurogenic locus notch homolog protein; TNFAIP3, tumor necrosis factor alpha-induced protein 3; TP53, tumor protein P53; TRAF3, tumor necrosis factor receptor-associated factor 3.