Starting from the model in [27], we further added some nodes based on literature (signals: M-CSF, HMGB1; receptors: M-CSFR, RAGE; intracellular components: IRF5, EGF, TNFα, TGFβ, HIF1α, Table S1a) which describe the mechanisms involved in the establishment of the interaction between NLC and CLL, such as receptor–ligand interaction (M-CSF - M-CSFR, HMGB1 - RAGE [37]) that are frequently present in tumoral environments. This evidence concerns the gene HMGB1 and B-cell chronic lymphocytic leukemia.