Proteomics identifies apoptotic markers as predictors of histological transformation in patients with follicular lymphoma.

Autor:	Enemark MBH; Department of Hematology, Aarhus University Hospital, Aarhus, Denmark.; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark., Wolter K; Department of Hematology, Aarhus University Hospital, Aarhus, Denmark., Campbell AJ; Department of Hematology, Aarhus University Hospital, Aarhus, Denmark., Andersen MD; Department of Hematology, Aarhus University Hospital, Aarhus, Denmark.; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark., Sørensen EF; Department of Hematology, Aarhus University Hospital, Aarhus, Denmark., Hybel TE; Department of Hematology, Aarhus University Hospital, Aarhus, Denmark.; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark., Madsen C; Department of Hematology, Aarhus University Hospital, Aarhus, Denmark., Lauridsen KL; Department of Pathology, Aarhus University Hospital, Aarhus, Denmark., Plesner TL; Department of Pathology, Copenhagen University Hospital, Copenhagen, Denmark., Hamilton-Dutoit SJ; Department of Pathology, Aarhus University Hospital, Aarhus, Denmark., Honoré B; Department of Biomedicine, Aarhus University, Aarhus, Denmark., Ludvigsen M; Department of Hematology, Aarhus University Hospital, Aarhus, Denmark.; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2023 Dec 26; Vol. 7 (24), pp. 7418-7432.
DOI:	10.1182/bloodadvances.2023011299
Abstrakt:	Follicular lymphoma (FL) is an indolent lymphoma with a generally favorable prognosis. However, histological transformation (HT) to a more aggressive disease leads to markedly inferior outcomes. This study aims to identify biological differences predictive of HT at the time of initial FL diagnosis. We show differential protein expression between diagnostic lymphoma samples from patients with subsequent HT (subsequently-transforming FL [st-FL]; n = 20) and patients without HT (nontransforming FL [nt-FL]; n = 34) by label-free quantification nano liquid chromatography-tandem mass spectrometry analysis. Protein profiles identified patients with high risk of HT. This was accompanied by disturbances in cellular pathways influencing apoptosis, the cytoskeleton, cell cycle, and immune processes. Comparisons between diagnostic st-FL samples and paired transformed FL (n = 20) samples demonstrated differential protein profiles and disrupted cellular pathways, indicating striking biological differences from the time of diagnosis up to HT. Immunohistochemical analysis of apoptotic proteins, CASP3, MCL1, BAX, BCL-xL, and BCL-rambo, confirmed higher expression levels in st-FL than in nt-FL samples (P < .001, P = .015, P = .003, P = .025, and P = .057, respectively). Moreover, all 5 markers were associated with shorter transformation-free survival (TFS; P < .001, P = .002, P < .001, P = .069, and P = .010, respectively). Notably, combining the expression of these proteins in a risk score revealed increasingly inferior TFS with an increasing number of positive markers. In conclusion, proteomics identified altered protein expression profiles (particularly apoptotic proteins) at the time of FL diagnosis, which predicted later transformation. (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
Databáze:	MEDLINE
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