Proteomic Profiling Differentiates Lymphoma Patients with and without Concurrent Myeloproliferative Neoplasia

Myeloproliferative neoplasia (MPN) and lymphoma are regarded as distinct diseases with different pathogeneses. However, patients that are diagnosed with both malignancies occur more frequently in the population than expected. This has led to the hypothesis that the two malignancies may, in some case...

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Autores principales: Johanne Marie Holst, Marie Beck Enemark, Martin Bjerregaard Pedersen, Kristina Lystlund Lauridsen, Trine Engelbrecht Hybel, Michael Roost Clausen, Henrik Frederiksen, Michael Boe Møller, Peter Nørgaard, Trine Lindhardt Plesner, Stephen Jacques Hamilton-Dutoit, Francesco d’Amore, Bent Honoré, Maja Ludvigsen
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Publicado: MDPI AG 2021
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spelling oai:doaj.org-article:09160659454e4d86851008de2cdea10b2021-11-11T15:33:53ZProteomic Profiling Differentiates Lymphoma Patients with and without Concurrent Myeloproliferative Neoplasia10.3390/cancers132155262072-6694https://doaj.org/article/09160659454e4d86851008de2cdea10b2021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5526https://doaj.org/toc/2072-6694Myeloproliferative neoplasia (MPN) and lymphoma are regarded as distinct diseases with different pathogeneses. However, patients that are diagnosed with both malignancies occur more frequently in the population than expected. This has led to the hypothesis that the two malignancies may, in some cases, be pathogenetically related. Using a mass spectrometry-based proteomic approach, we show that pre-treatment lymphoma samples from patients with both MPN and lymphoma, either angioimmunoblastic T-cell lymphoma (MPN-AITL) or diffuse large B-cell lymphoma (MPN-DLBCL), show differences in protein expression compared with reference AITL or DLBCL samples from patients without MPN. A distinct clustering of samples from patients with and without MPN was evident for both AITL and DLBCL. Regarding MPN-AITL, a pathway analysis revealed disturbances of cellular respiration as well as oxidative metabolism, and an immunohistochemical evaluation further demonstrated the differential expression of citrate synthase and <i>DNAJA2</i> protein (<i>p</i> = 0.007 and <i>p</i> = 0.015). Interestingly, <i>IDH2</i> protein also showed differential expression in the MPN-AITL patients, which contributes to the growing evidence of this protein’s role in both myeloid neoplasia and AITL. In MPN-DLBCL, the disturbed pathways included a significant downregulation of protein synthesis as well as a perturbation of signal transduction. These results imply an underlying disturbance of tumor molecular biology, and in turn an alternative pathogenesis for tumors in these patients with both myeloid and lymphoid malignancies.Johanne Marie HolstMarie Beck EnemarkMartin Bjerregaard PedersenKristina Lystlund LauridsenTrine Engelbrecht HybelMichael Roost ClausenHenrik FrederiksenMichael Boe MøllerPeter NørgaardTrine Lindhardt PlesnerStephen Jacques Hamilton-DutoitFrancesco d’AmoreBent HonoréMaja LudvigsenMDPI AGarticleangioimmunoblastic T-cell lymphoma (AITL)diffuse large B-cell lymphoma (DLBCL)myeloproliferative neoplasia (MPN)proteomicsNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5526, p 5526 (2021)
institution DOAJ
collection DOAJ
language EN
topic angioimmunoblastic T-cell lymphoma (AITL)
diffuse large B-cell lymphoma (DLBCL)
myeloproliferative neoplasia (MPN)
proteomics
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
spellingShingle angioimmunoblastic T-cell lymphoma (AITL)
diffuse large B-cell lymphoma (DLBCL)
myeloproliferative neoplasia (MPN)
proteomics
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Johanne Marie Holst
Marie Beck Enemark
Martin Bjerregaard Pedersen
Kristina Lystlund Lauridsen
Trine Engelbrecht Hybel
Michael Roost Clausen
Henrik Frederiksen
Michael Boe Møller
Peter Nørgaard
Trine Lindhardt Plesner
Stephen Jacques Hamilton-Dutoit
Francesco d’Amore
Bent Honoré
Maja Ludvigsen
Proteomic Profiling Differentiates Lymphoma Patients with and without Concurrent Myeloproliferative Neoplasia
description Myeloproliferative neoplasia (MPN) and lymphoma are regarded as distinct diseases with different pathogeneses. However, patients that are diagnosed with both malignancies occur more frequently in the population than expected. This has led to the hypothesis that the two malignancies may, in some cases, be pathogenetically related. Using a mass spectrometry-based proteomic approach, we show that pre-treatment lymphoma samples from patients with both MPN and lymphoma, either angioimmunoblastic T-cell lymphoma (MPN-AITL) or diffuse large B-cell lymphoma (MPN-DLBCL), show differences in protein expression compared with reference AITL or DLBCL samples from patients without MPN. A distinct clustering of samples from patients with and without MPN was evident for both AITL and DLBCL. Regarding MPN-AITL, a pathway analysis revealed disturbances of cellular respiration as well as oxidative metabolism, and an immunohistochemical evaluation further demonstrated the differential expression of citrate synthase and <i>DNAJA2</i> protein (<i>p</i> = 0.007 and <i>p</i> = 0.015). Interestingly, <i>IDH2</i> protein also showed differential expression in the MPN-AITL patients, which contributes to the growing evidence of this protein’s role in both myeloid neoplasia and AITL. In MPN-DLBCL, the disturbed pathways included a significant downregulation of protein synthesis as well as a perturbation of signal transduction. These results imply an underlying disturbance of tumor molecular biology, and in turn an alternative pathogenesis for tumors in these patients with both myeloid and lymphoid malignancies.
format article
author Johanne Marie Holst
Marie Beck Enemark
Martin Bjerregaard Pedersen
Kristina Lystlund Lauridsen
Trine Engelbrecht Hybel
Michael Roost Clausen
Henrik Frederiksen
Michael Boe Møller
Peter Nørgaard
Trine Lindhardt Plesner
Stephen Jacques Hamilton-Dutoit
Francesco d’Amore
Bent Honoré
Maja Ludvigsen
author_facet Johanne Marie Holst
Marie Beck Enemark
Martin Bjerregaard Pedersen
Kristina Lystlund Lauridsen
Trine Engelbrecht Hybel
Michael Roost Clausen
Henrik Frederiksen
Michael Boe Møller
Peter Nørgaard
Trine Lindhardt Plesner
Stephen Jacques Hamilton-Dutoit
Francesco d’Amore
Bent Honoré
Maja Ludvigsen
author_sort Johanne Marie Holst
title Proteomic Profiling Differentiates Lymphoma Patients with and without Concurrent Myeloproliferative Neoplasia
title_short Proteomic Profiling Differentiates Lymphoma Patients with and without Concurrent Myeloproliferative Neoplasia
title_full Proteomic Profiling Differentiates Lymphoma Patients with and without Concurrent Myeloproliferative Neoplasia
title_fullStr Proteomic Profiling Differentiates Lymphoma Patients with and without Concurrent Myeloproliferative Neoplasia
title_full_unstemmed Proteomic Profiling Differentiates Lymphoma Patients with and without Concurrent Myeloproliferative Neoplasia
title_sort proteomic profiling differentiates lymphoma patients with and without concurrent myeloproliferative neoplasia
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/09160659454e4d86851008de2cdea10b
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