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CONTATTA
Evoluzione patologica
La linfomagenesi del linfoma follicolare è un complesso processo che si verifica in molte fasi della differenziazione dei linfociti B.
- Traslocazione t(14;18) in cellule pre-B. Nel midollo osseo si verifica la traslocazione cromosomica t(14;18)(q32;q21) in cellule allo stadio pre‑B (caratteristica presente in circa il 90% dei pazienti), portando alla sovraespressione costitutiva della proteina anti-apoptotica BCL‑2. L’espressione forzata di BCL‑2 offre un vantaggio in termini di sopravvivenza alle cellule portatrici di questa mutazione.
- Arresto dello sviluppo in cellule B. Quando le cellule con traslocazione cromosomica t(14;18) vanno incontro a maturazione nel centro germinativo, possono uscirne come linfociti B di memoria switched IgM o andare incontro ad un arresto dello sviluppo, dando origine a cellule linfoma follicolare-simili (FL-like cells, FLLC) caratterizzate da fenotipo centroblasto‑simile o centrocita-simile. Queste cellule sono presenti nella maggior parte degli individui sani e possono non progredire mai verso il linfoma follicolare.
- Fase pre-maligna. Ad ogni passaggio dello sviluppo, le cellule portatrici di traslocazione t(14;18) possono diffondersi ampiamente e spostarsi tra follicoli, sangue e midollo osseo. Possono anche rientrare nei centri germinativi dopo aver reincontrato l’antigene o dopo un altro segnale ancora non identificato. Si ipotizza che la loro instabilità genetica insieme ad un microambiente di supporto, induca gradualmente espansione clonale ed acquisizione di ulteriori alterazioni genetiche.
- Patologia conclamata. L’evoluzione nel corso del tempo può portare a progressione verso stadi maligni precoci (neoplasia follicolare in situ, ISFN, o linfoma follicolare con coinvolgimento parziale, PFL) fino a giungere al linfoma follicolare conclamato.
M-IT-00001038
Info utili
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Bibliografia
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