Mechanisms of transformation from nodular lymphocyte predominant Hodgkin lymphoma into diffuse large B cell lymphoma
Final Report Abstract
In this project we were able to identify several newly mutated genes in nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) as well as in T-cell/histiocyte rich large B-cell lymphoma (THRLBCL). Concerning the transformation of NLPHL into aggressive lymphomas we found that mutations in the DNA repair genes ATM, NPAT and TP53 and chromothripsislike events were associated with transformation. Gene expression profiling revealed that diffuse large B-cell lymphoma transformed from NLPHL have a strong and active PD-L1 signaling, which could also be implemented in future treatment strategies. We only observed minor differences in mutation patterns between NLPHL and THRLBCL, which is an aggressive lymphoma. This further emphasizes the very close relationship between both lymphoma entities. On the side we could clarify that progressively transformed germinal centres are frequently associated with an increased number of IgG4-positive plasma cells and we could find further morphological parameters that help to distinguish between PTGC and NLPHL.
Publications
- Immunoarchitectural patterns of progressive transformation of germinal centers with and without nodular lymphocyte predominant Hodgkin lymphoma. Hum Pathol. 46(11):1655-61. 2015
Hartmann S, Winkelmann R, Metcalf RA,Treetipsatit J, Warnke RA, Natkunam Y, Hansmann ML
(See online at https://doi.org/10.1016/j.humpath.2015.07.006) - A strong host response and lack of MYC expression are characteristic for diffuse large B cell lymphoma transformed from nodular lymphocyte predominant Hodgkin lymphoma. Oncotarget 7(44):72197-72210. 2016
Schuhmacher B, Rengstl B, Döring C, Bein J, Newrzela S, Brunnberg U, Kvasnicka HM, Vornanen M, Küppers R, Hansmann M-L, Hartmann S
(See online at https://doi.org/10.18632/oncotarget.12363) - Highly recurrent mutations of SGK1, DUSP2 and JUNB in nodular lymphocyte predominant Hodgkin lymphoma. Leukemia. 30(4):844-53. 2016
Hartmann S, Schuhmacher B, Rausch T, Fuller L, Döring C, Weniger M, Lollies A, Weiser C, Thurner L, Rengstl B, Brunnberg U, Vornanen M, Pfreundschuh M, Benes V, Küppers R, Newrzela S, Hansmann ML
(See online at https://doi.org/10.1038/leu.2015.328) - Atypical variants of nodular lymphocyte-predominant Hodgkin lymphoma show low microvessel density and vessels of distention type. Hum Pathol. 60:129-136. 2017
Scheidt V, Hansmann ML, Schuhmacher B, Döring C, Hartmann S
(See online at https://doi.org/10.1016/j.humpath.2016.10.008) - A high number of IgG4-positive plasma cells rules out nodular lymphocyte predominant Hodgkin lymphoma. Virchows Arch. 2018 Dec;473(6):759-764
Kiil K, Bein J, Schuhmacher B, Thurner L, Schneider M, Hansmann ML, Hartmann S
(See online at https://doi.org/10.1007/s00428-018-2460-8)
