Proteomic profiling identifies classic Hodgkin lymphoma patients at risk of bleomycin pulmonary toxicity

Maja Dam Andersen; Katharina Wolter; Marie Hairing Enemark; Kristina Lystlund Lauridsen; Stephen Jacques Hamilton-Dutoit; Jørn Starklint; Francesco d’Amore; Maja Ludvigsen; Bent Honoré; Peter Kamper

doi:10.1080/10428194.2024.2434170

Proteomic profiling identifies classic Hodgkin lymphoma patients at risk of bleomycin pulmonary toxicity

Maja Dam Andersen^*, Katharina Wolter, Marie Hairing Enemark, Kristina Lystlund Lauridsen, Stephen Jacques Hamilton-Dutoit, Jørn Starklint, Francesco d’Amore, Maja Ludvigsen, Bent Honoré^*, Peter Kamper

^*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

Abstract

Advances in treating classic Hodgkin lymphoma (cHL) have improved cure rates, with overall survival exceeding 80%, resulting in a growing population of survivors at risk of long-term complications, particularly cardiac and pulmonary toxicity. Bleomycin, a key component of combination chemotherapy, is associated with bleomycin-induced pulmonary toxicity (BPT). Using label-free quantification nano liquid chromatography-tandem mass spectrometry, protein expression in diagnostic lymphoma samples from patients with and without BPT was compared. Results showed differential protein expression and disrupted cellular pathways, suggesting biological differences in BPT risk. Immunohistochemical analysis revealed higher expression of JAK3, BID, and MMP9, and lower expression of CD20, TPD52, and PIK3R4 in patients with BPT. High BID and low CD20 expression were associated with inferior overall survival, while high BID and low JAK3 and CD20 expression were linked to poorer progression-free survival. These findings highlight altered protein profiles in pretreatment cHL biopsies associated with BPT development.

Originalsprog	Engelsk
Tidsskrift	Leukemia and Lymphoma
Vol/bind	66
Nummer	4
Sider (fra-til)	656-667
Antal sider	12
ISSN	1042-8194
DOI	https://doi.org/10.1080/10428194.2024.2434170
Status	Udgivet - 2025

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title = "Proteomic profiling identifies classic Hodgkin lymphoma patients at risk of bleomycin pulmonary toxicity",

abstract = "Advances in treating classic Hodgkin lymphoma (cHL) have improved cure rates, with overall survival exceeding 80%, resulting in a growing population of survivors at risk of long-term complications, particularly cardiac and pulmonary toxicity. Bleomycin, a key component of combination chemotherapy, is associated with bleomycin-induced pulmonary toxicity (BPT). Using label-free quantification nano liquid chromatography-tandem mass spectrometry, protein expression in diagnostic lymphoma samples from patients with and without BPT was compared. Results showed differential protein expression and disrupted cellular pathways, suggesting biological differences in BPT risk. Immunohistochemical analysis revealed higher expression of JAK3, BID, and MMP9, and lower expression of CD20, TPD52, and PIK3R4 in patients with BPT. High BID and low CD20 expression were associated with inferior overall survival, while high BID and low JAK3 and CD20 expression were linked to poorer progression-free survival. These findings highlight altered protein profiles in pretreatment cHL biopsies associated with BPT development.",

keywords = "Bleomycin pulmonary toxicity (BPT), classic Hodgkin lymphoma (cHL), FFPE-tissue, prognosis, proteomics",

author = "Andersen, {Maja Dam} and Katharina Wolter and Enemark, {Marie Hairing} and Lauridsen, {Kristina Lystlund} and Hamilton-Dutoit, {Stephen Jacques} and J{\o}rn Starklint and Francesco d{\textquoteright}Amore and Maja Ludvigsen and Bent Honor{\'e} and Peter Kamper",

note = "Publisher Copyright: {\textcopyright} 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.",

year = "2025",

doi = "10.1080/10428194.2024.2434170",

language = "English",

volume = "66",

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TY - JOUR

T1 - Proteomic profiling identifies classic Hodgkin lymphoma patients at risk of bleomycin pulmonary toxicity

AU - Andersen, Maja Dam

AU - Wolter, Katharina

AU - Enemark, Marie Hairing

AU - Lauridsen, Kristina Lystlund

AU - Hamilton-Dutoit, Stephen Jacques

AU - Starklint, Jørn

AU - d’Amore, Francesco

AU - Ludvigsen, Maja

AU - Honoré, Bent

AU - Kamper, Peter

PY - 2025

Y1 - 2025

N2 - Advances in treating classic Hodgkin lymphoma (cHL) have improved cure rates, with overall survival exceeding 80%, resulting in a growing population of survivors at risk of long-term complications, particularly cardiac and pulmonary toxicity. Bleomycin, a key component of combination chemotherapy, is associated with bleomycin-induced pulmonary toxicity (BPT). Using label-free quantification nano liquid chromatography-tandem mass spectrometry, protein expression in diagnostic lymphoma samples from patients with and without BPT was compared. Results showed differential protein expression and disrupted cellular pathways, suggesting biological differences in BPT risk. Immunohistochemical analysis revealed higher expression of JAK3, BID, and MMP9, and lower expression of CD20, TPD52, and PIK3R4 in patients with BPT. High BID and low CD20 expression were associated with inferior overall survival, while high BID and low JAK3 and CD20 expression were linked to poorer progression-free survival. These findings highlight altered protein profiles in pretreatment cHL biopsies associated with BPT development.

AB - Advances in treating classic Hodgkin lymphoma (cHL) have improved cure rates, with overall survival exceeding 80%, resulting in a growing population of survivors at risk of long-term complications, particularly cardiac and pulmonary toxicity. Bleomycin, a key component of combination chemotherapy, is associated with bleomycin-induced pulmonary toxicity (BPT). Using label-free quantification nano liquid chromatography-tandem mass spectrometry, protein expression in diagnostic lymphoma samples from patients with and without BPT was compared. Results showed differential protein expression and disrupted cellular pathways, suggesting biological differences in BPT risk. Immunohistochemical analysis revealed higher expression of JAK3, BID, and MMP9, and lower expression of CD20, TPD52, and PIK3R4 in patients with BPT. High BID and low CD20 expression were associated with inferior overall survival, while high BID and low JAK3 and CD20 expression were linked to poorer progression-free survival. These findings highlight altered protein profiles in pretreatment cHL biopsies associated with BPT development.

KW - Bleomycin pulmonary toxicity (BPT)

KW - classic Hodgkin lymphoma (cHL)

KW - FFPE-tissue

KW - prognosis

KW - proteomics

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U2 - 10.1080/10428194.2024.2434170

DO - 10.1080/10428194.2024.2434170

M3 - Journal article

C2 - 39625996

AN - SCOPUS:85211113995

SN - 1042-8194

VL - 66

SP - 656

EP - 667

JO - Leukemia and Lymphoma

JF - Leukemia and Lymphoma

IS - 4

ER -

Proteomic profiling identifies classic Hodgkin lymphoma patients at risk of bleomycin pulmonary toxicity

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