PMID- 36519324
OWN - NLM
STAT- MEDLINE
DCOM- 20230404
LR  - 20230411
IS  - 1592-8721 (Electronic)
IS  - 0390-6078 (Print)
IS  - 0390-6078 (Linking)
VI  - 108
IP  - 4
DP  - 2023 Apr 1
TI  - 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 highrisk factors.
PG  - 1092-1104
LID - 10.3324/haematol.2022.281420 [doi]
AB  - 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.
FAU - Gerdtsson, Anna Sandstrom
AU  - Gerdtsson AS
AD  - Department of Immunotechnology, Lund University.
FAU - Matos Rodrigues, Joana de
AU  - Matos Rodrigues J
AD  - Department of Immunotechnology, Lund University.
FAU - Eskelund, Christian Winther
AU  - Eskelund CW
AD  - Department of Hematology, Rigshospitalet, Copenhagen.
FAU - Husby, Simon
AU  - Husby S
AD  - Department of Hematology, Rigshospitalet, Copenhagen.
FAU - Gronbaek, Kirsten
AU  - Gronbaek K
AD  - Department of Hematology, Rigshospitalet, Copenhagen.
FAU - Raty, Riikka
AU  - Raty R
AD  - Department of Hematology, Helsinki University Hospital, Helsinki.
FAU - Kolstad, Arne
AU  - Kolstad A
AD  - Department of Oncology, Oslo University Hospital, Oslo.
FAU - Geisler, Christian
AU  - Geisler C
AD  - Department of Hematology, Rigshospitalet, Copenhagen.
FAU - Porwit, Anna
AU  - Porwit A
AD  - Department of Clinical Sciences, Oncology and Pathology, Lund University, Lund.
FAU - Jerkeman, Mats
AU  - Jerkeman M
AD  - Department of Oncology, Lund University Hospital, Lund.
FAU - Ek, Sara
AU  - Ek S
AD  - Department of Immunotechnology, Lund University. sara.ek@immun.lth.se.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230401
PL  - Italy
TA  - Haematologica
JT  - Haematologica
JID - 0417435
RN  - EC 2.3.1.21 (Carnitine O-Palmitoyltransferase)
RN  - 0 (Immunologic Factors)
RN  - 0 (Fatty Acids)
SB  - IM
MH  - Adult
MH  - Humans
MH  - *Lymphoma, Mantle-Cell/drug therapy/genetics
MH  - Carnitine O-Palmitoyltransferase/genetics
MH  - Risk Assessment
MH  - Prognosis
MH  - Neoplasm Recurrence, Local
MH  - Immunologic Factors/therapeutic use
MH  - Fatty Acids/therapeutic use
PMC - PMC10071121
EDAT- 2022/12/16 06:00
MHDA- 2023/04/04 06:42
PMCR- 2022/12/15
CRDT- 2022/12/15 03:35
PHST- 2022/05/24 00:00 [received]
PHST- 2023/04/04 06:42 [medline]
PHST- 2022/12/16 06:00 [pubmed]
PHST- 2022/12/15 03:35 [entrez]
PHST- 2022/12/15 00:00 [pmc-release]
AID - 10.3324/haematol.2022.281420 [doi]
PST - epublish
SO  - Haematologica. 2023 Apr 1;108(4):1092-1104. doi: 10.3324/haematol.2022.281420.