Deciphering the first steps of follicular lymphomagenesis: a comprehensive genetic analysis of follicular lymphoma in situ (in situ follicular neoplasia) and its progression
Final Report Abstract
In the project, we were able to show for the first time that in situ follicular neoplasia (ISFN) occurring in patients with B-cell lymphoma is a clonally related precursor lesion not only for follicular lymphoma, but also for aggressive B cell lymphoma (DLBCL and so-called double/triple hit lymphoma) carrying a t(14;18) translocation. Already at this early preclinical stage, ISFN shows N-glycosylation motifs in the rearranged IGH enabling antigen independent BCR signalling and contains a significant number of secondary driver mutations in well-known genes involved in FL pathogenesis, indicating that other factors such as a tumor supportive microenvironment likely play a role in progression to clinically manifest lymphoma. Furthermore, the observation of so-called branched evolution indicates that ISFN may persist for a long time and likely can give rise to recurrences. These data help us to understand better the initial phases of lymphoma development and may provide future avenues for research and new approaches for therapeutic targeting of malignant lymphoma.
Publications
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CREBBP gene mutations are frequently detected in in situ follicular neoplasia. Blood. 2018 Dec 20;132(25):2687-2690
Schmidt J, Ramis-Zaldivar JE, Bonzheim I, Steinhilber J, Müller I, Haake A, Yu SC, Raffeld M, Fend F, Salaverria I, Siebert R, Jaffe ES, Quintanilla-Martinez L
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t(14;18)-positive B cells: is it seed or soil? Blood. 2018 Oct 18;132(16):1631-1632 (Commentary)
Jaffe ES, Quintanilla-Martinez L
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Clonally related duodenal-type follicular lymphoma and in situ follicular neoplasia. Haematologica. 2019 Nov;104(11):e537-e539
Nann D, Bonzheim I, Müller I, Mankel B, Quintanilla-Martínez L, Sipos B, Fend F
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Follicular lymphoma t(14;18)-negative is genetically a heterogeneous disease. Blood Adv. 2020 Nov 24;4(22):5652-5665
Nann D, Ramis-Zaldivar JE, Müller I, Gonzalez-Farre B, Schmidt J, Egan C, Salmeron- Villalobos J, Clot G, Mattern S, Otto F, Mankel B, Colomer D, Balagué O, Szablewski V, Lome- Maldonado C, Leoncini L, Dojcinov S, Chott A, Copie-Bergman C, Bonzheim I, Fend F, Jaffe ES, Campo E, Salaverria I, Quintanilla-Martinez L
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Genetic evolution of in situ follicular neoplasia to aggressive B-cell lymphoma of germinal center subtype. Haematologica. 2020 Aug 27
Vogelsberg A, Steinhilber J, Mankel B, Federmann B, Schmidt J, Montes-Mojarro IA, Hüttl K, Rodriguez-Pinilla M, Baskaran P, Nahnsen S, Piris MA, Ott G, Quintanilla-Martinez L, Bonzheim I, Fend F
