TRAJECTORIES OF LYMPHOMAGENESIS

In the last 10 years, we have dramatically increased our knowledge on (epi)genetics, etiology, and dynamics of Follicular lymphoma (FL). that period, it has become widely accepted preclinical subclinical development phases FL, taking years from emergence a unique t(14;18)+ B cell in BM to detection symptomatic LN full its descendants aggregated FL follicles, involves multiple transits Mem-like cells through sequential GC. The remarkable plasticity longevity normal Mem cells, coupled with mutation-prone proliferative states GC provide fertile grounds for transformation into malignant neoplasia. But until very recently, common view was GC-Mem dynamic cycle would stop at one stage when ‘freeze’ their final overt state. Among others, single-cell analyses are challenging concept, portraying model where GC<->Mem continue fuel progression, likely relapses, disease stage. revised model, not ‘frozen,’ but as functionally plastic pre-malignant counterparts, circulating follicle next, another or BM. With recent advances methods spatial genomics, many unresolved questions physiopathology now within reach. What drives state transitions cells? How do genetics affect states? integrate signals microenvironment genetically rewired signaling networks perturbed epigenetics? will translate those new biological concepts clinical advances? Can rewire respond differently microenvironment? purge all organs they may home? upcoming drawing comprehensive functional picture ecosystem holds great promise address unmet medical needs this complex lymphoma. Keywords: epigenomics, other -omics, tumor biology heterogeneity No conflicts interests pertinent abstract.