Overexpression of the key metabolic protein CPT1A defines mantle cell lymphoma patients with poor response to standard high-dose chemotherapy independent of MIPI and complement established high-risk factors

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  • Anna Sandström Gerdtsson
  • Joana de Matos Rodrigues
  • Christian Winther Eskelund
  • Husby, Simon
  • Grønbæk, Kirsten
  • Riikka Räty
  • Arne Kolstad
  • Christian Geisler
  • Anna Porwit
  • Mats Jerkeman
  • Sara Ek

The variable outcome to standard immunochemotherapy for mantle cell lymphoma (MCL) patients is a clinical challenge. Established risk factors, including high MCL International Prognostic Index (MIPI), high proliferation (Ki-67), non-classic (blastoid/pleomorphic) morphology, and mutated TP53, only partly identify patients in need of alternative treatment. Deepened understanding of biological factors that influence time to progression and relapse would allow for an improved stratification, and identification of novel targets for high-risk patients. We performed gene expression analyses to identify pathways and genes associated with outcome in a cohort of homogeneously treated patients. In addition to deregulated proliferation, we show that thermogenesis, fatty acid degradation and oxidative phosphorylation are altered in patients with poor survival, and that high expression of carnitine palmitoyltransferase 1A (CPT1A), an enzyme involved in fatty acid degradation, can specifically identify high-risk patients independent of the established high-risk factors. We suggest that complementary investigations of metabolism may increase the accuracy of patient stratification and that immunohistochemistry-based assessment of CPT1A can contribute to defining high-risk MCL.

OriginalsprogEngelsk
TidsskriftHaematologica
Vol/bind108
Udgave nummer4
Sider (fra-til)1092-1104
Antal sider13
ISSN0390-6078
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
The authors would like to thank the Nordic lymphoma group, and specifically the Nordic MCL network; Lina Olsson and May Hassan at the SpatialOmics@LU core facility at the Department of Immunotechnology, Lund University for assisting with expression analysis; Björn Nodin at the Department of Clinical Studies, Lund University for assisting with tissue cuts and IHC. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement N 754299, Cancerfonden (2016/465, 19 0309Pj and 21 1561 Pj), Mats Paulssons Stiftelse för forskning, innovation och samhällsbyggande, Stiftelsen Stefan Paulssons cancerfond, and CREATE Health. All financial support was granted to SE.

Publisher Copyright:
©2023 Ferrata Storti Foundation.

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