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.

Original languageEnglish
JournalHaematologica
Volume108
Issue number4
Pages (from-to)1092-1104
Number of pages13
ISSN0390-6078
DOIs
Publication statusPublished - 2023

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