TY - JOUR
T1 - Expression patterns and prognostic potential of circular RNAs in mantle cell lymphoma
T2 - a study of younger patients from the MCL2 and MCL3 clinical trials
AU - Dahl, Mette
AU - Husby, Simon
AU - Eskelund, Christian W
AU - Besenbacher, Søren
AU - Fjelstrup, Søren
AU - Côme, Christophe
AU - Ek, Sara
AU - Kolstad, Arne
AU - Räty, Riikka
AU - Jerkeman, Mats
AU - Geisler, Christian H
AU - Kjems, Jørgen
AU - Kristensen, Lasse S
AU - Grønbæk, Kirsten
N1 - Correction: https://doi.org/10.1038/s41375-022-01526-z
© 2021. The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
U2 - 10.1038/s41375-021-01311-4
DO - 10.1038/s41375-021-01311-4
M3 - Journal article
C2 - 34244612
VL - 36
SP - 177
EP - 188
JO - Leukemia
JF - Leukemia
SN - 0887-6924
ER -