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Expression patterns and prognostic potential of circular RNAs in mantle cell lymphoma : a study of younger patients from the MCL2 and MCL3 clinical trials

Dahl, Mette (author)
University of Copenhagen,Copenhagen University Hospital
Husby, Simon (author)
Copenhagen University Hospital,University of Copenhagen
Eskelund, Christian W. (author)
University of Copenhagen,Copenhagen University Hospital
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Besenbacher, Søren (author)
Aarhus University
Fjelstrup, Søren (author)
Aarhus University
Côme, Christophe (author)
University of Copenhagen,Copenhagen University Hospital
Ek, Sara (author)
Lund University,Lunds universitet,Institutionen för immunteknologi,Institutioner vid LTH,Lunds Tekniska Högskola,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Department of Immunotechnology,Departments at LTH,Faculty of Engineering, LTH,LUCC: Lund University Cancer Centre,Other Strong Research Environments
Kolstad, Arne (author)
Norwegian Radium Hospital
Räty, Riikka (author)
Helsinki University Central Hospital
Jerkeman, Mats (author)
Lund University,Lunds universitet,Lymfom - Klinisk forskning,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Lymphoma - Clinical Research,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
Geisler, Christian H. (author)
Copenhagen University Hospital
Kjems, Jørgen (author)
Aarhus University
Kristensen, Lasse S. (author)
Aarhus University
Grønbæk, Kirsten (author)
University of Copenhagen,Copenhagen University Hospital
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 (creator_code:org_t)
2021-07-09
2022
English.
In: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 36:1, s. 177-188
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http://dx.doi.org/10...
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Mantle cell lymphoma (MCL) is characterized by marked differences in outcome, emphasizing the need for strong prognostic biomarkers. Here, we explore expression patterns and prognostic relevance of circular RNAs (circRNAs), a group of endogenous non-coding RNA molecules, in MCL. We profiled the circRNA expression landscape using RNA-sequencing and explored the prognostic potential of 40 abundant circRNAs in samples from the Nordic MCL2 and MCL3 clinical trials, using NanoString nCounter Technology. We report a circRNA-based signature (circSCORE) developed in the training cohort MCL2 that is highly predictive of time to progression (TTP) and lymphoma-specific survival (LSS). The dismal outcome observed in the large proportion of patients assigned to the circSCORE high-risk group was confirmed in the independent validation cohort MCL3, both in terms of TTP (HR 3.0; P = 0.0004) and LSS (HR 3.6; P = 0.001). In Cox multiple regression analysis incorporating MIPI, Ki67 index, blastoid morphology and presence of TP53 mutations, circSCORE retained prognostic significance for TTP (HR 3.2; P = 0.01) and LSS (HR 4.6; P = 0.01). In conclusion, circRNAs are promising prognostic biomarkers in MCL and circSCORE improves identification of high-risk disease among younger patients treated with cytarabine-containing chemoimmunotherapy and autologous stem cell transplant.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

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