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

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 immunohisto-chemistry-based assessment of CPT1A can contribute to defining high-risk MCL.

Automated summary

The variable response to standard immunochemotherapy in patients with mantle cell lymphoma (MCL) remains a clinical challenge. Established risk factors only partially identify patients requiring alternative treatment. Gene expression analyses revealed alterations in thermogenesis, fatty acid degradation, and oxidative phosphorylation in patients with poor survival, and high expression of CPT1A can specifically identify high-risk MCL patients. Complementary investigations of metabolism and immunohistochemistry-based assessment of CPT1A may improve patient stratification.