TY - JOUR
T1 - Immunoglobulin kappa deleting element rearrangements are candidate targets for minimal residual disease evaluation in mantle cell lymphoma
AU - Fondazione Italiana Linfomi (FIL) MRD Network
AU - Della Starza, Irene
AU - De Novi, Lucia Anna
AU - Cavalli, Marzia
AU - Novelli, Noemi
AU - Soscia, Roberta
AU - Genuardi, Elisa
AU - Mantoan, Barbara
AU - Drandi, Daniela
AU - Ferrante, Martina
AU - Monitillo, Luigia
AU - Barbero, Daniela
AU - Ciabatti, Elena
AU - Grassi, Susanna
AU - Bomben, Riccardo
AU - Degan, Massimo
AU - Gattei, Valter
AU - Galimberti, Sara
AU - Di Rocco, Alice
AU - Martelli, Maurizio
AU - Cortelazzo, Sergio
AU - Guarini, Anna
AU - Foà, Robin
AU - Ladetto, Marco
AU - Ferrero, Simone
AU - Del Giudice, Ilaria
N1 - Funding Information:
The authors wish to thank: Fondi di Ricerca Locale, Universit? degli Studi di Torino, Italy; Fondazione Neoplasie Del Sangue (Fo.Ne.Sa), Torino, Italy; Fondazione CRT (projects code: 2016.0677, 2018.1284), Torino, Italy; Associazione Italiana per la Ricerca sul Cancro (AIRC), Metastases Special Program (N? 21,198), Milano, Italy (Robin Fo?); Progetti di Ricerca di Ateneo 2017, Sapienza University, Roma, Italy (Alice Di Rocco).
Publisher Copyright:
© 2020 John Wiley & Sons Ltd.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2020/12
Y1 - 2020/12
N2 - Minimal residual disease (MRD) assessment is of high clinical relevance in patients with mantle cell lymphoma (MCL). In mature B-cell malignancies, the presence of somatic hypermutations (SHM) in Variable-Diversity-Joining Heavy chain (VDJH) rearrangements leads to frequent mismatches between primers, probes, and the target, thus impairing tumor cells quantification. Alternative targets, such as immunoglobulin kappa-deleting-element (IGK-Kde) rearrangements, might be suitable for MRD detection. We aimed at evaluating the applicability of IGK-Kde rearrangements for MRD quantification in MCL patients by real-time quantitative polymerase chain reaction (RQ-PCR)/digital-droplet-PCR (ddPCR). IGK screening was performed on bone marrow samples from two cohorts: the first from Turin (22 patients enrolled in the FIL-MCL0208 trial, NCT02354313) and the second from Rome (15 patients). IGK-Kde rearrangements were found in 76% (28/37) of cases, representing the sole molecular marker in 73% (8/11) of IGH-BCL1/IGH negative cases. MRD RQ-PCR monitoring was possible in 57% (16/28) of cases, showing a 100% concordance with the conventional targets. However, the frequent background amplification affected the sensitivity of the assay, that was lower in MCL compared to acute lymphoblastic leukemia and in line with multiple myeloma published results. ddPCR had a good concordance with RQ-PCR and it might help to identify false positive/negative results. From a clinical perspective, we suggest that IGK-Kde can be a candidate target for MRD monitoring and deserves a validation of its predictive value in prospective MCL series.
AB - Minimal residual disease (MRD) assessment is of high clinical relevance in patients with mantle cell lymphoma (MCL). In mature B-cell malignancies, the presence of somatic hypermutations (SHM) in Variable-Diversity-Joining Heavy chain (VDJH) rearrangements leads to frequent mismatches between primers, probes, and the target, thus impairing tumor cells quantification. Alternative targets, such as immunoglobulin kappa-deleting-element (IGK-Kde) rearrangements, might be suitable for MRD detection. We aimed at evaluating the applicability of IGK-Kde rearrangements for MRD quantification in MCL patients by real-time quantitative polymerase chain reaction (RQ-PCR)/digital-droplet-PCR (ddPCR). IGK screening was performed on bone marrow samples from two cohorts: the first from Turin (22 patients enrolled in the FIL-MCL0208 trial, NCT02354313) and the second from Rome (15 patients). IGK-Kde rearrangements were found in 76% (28/37) of cases, representing the sole molecular marker in 73% (8/11) of IGH-BCL1/IGH negative cases. MRD RQ-PCR monitoring was possible in 57% (16/28) of cases, showing a 100% concordance with the conventional targets. However, the frequent background amplification affected the sensitivity of the assay, that was lower in MCL compared to acute lymphoblastic leukemia and in line with multiple myeloma published results. ddPCR had a good concordance with RQ-PCR and it might help to identify false positive/negative results. From a clinical perspective, we suggest that IGK-Kde can be a candidate target for MRD monitoring and deserves a validation of its predictive value in prospective MCL series.
KW - FIL
KW - IGK-Kde rearrangement
KW - MRD
KW - non-Hodgkin lymphoma
UR - http://www.scopus.com/inward/record.url?scp=85089903878&partnerID=8YFLogxK
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U2 - 10.1002/hon.2792
DO - 10.1002/hon.2792
M3 - Article
C2 - 32816326
AN - SCOPUS:85089903878
VL - 38
SP - 698
EP - 704
JO - Hematological Oncology
JF - Hematological Oncology
SN - 0278-0232
IS - 5
ER -