MYD88<sup>L265P</sup> Detection in IgM Monoclonal Gammopathies: Methodological Considerations for Routine Implementation
In IgM monoclonal gammopathies MYD88<sup>L265P</sup> is a prognostic and predictive biomarker of therapy response. MYD88<sup>L265P</sup> detection is mainly performed by allele-specific quantitative PCR (ASqPCR), however recently, droplet digital PCR (ddPCR) has been proved t...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-04-01
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| Series: | Diagnostics |
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| Online Access: | https://www.mdpi.com/2075-4418/11/5/779 |
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| author | Martina Ferrante Daniela Furlan Silvia Zibellini Michela Borriero Chiara Candido Nora Sahnane Silvia Uccella Elisa Genuardi Beatrice Alessandria Benedetta Bianchi Barbara Mora Daniele Grimaldi Irene Defrancesco Cristina Jiménez Federica Cavallo Dario Ferrero Irene Dogliotti Michele Merli Marzia Varettoni Simone Ferrero Daniela Drandi |
| author_facet | Martina Ferrante Daniela Furlan Silvia Zibellini Michela Borriero Chiara Candido Nora Sahnane Silvia Uccella Elisa Genuardi Beatrice Alessandria Benedetta Bianchi Barbara Mora Daniele Grimaldi Irene Defrancesco Cristina Jiménez Federica Cavallo Dario Ferrero Irene Dogliotti Michele Merli Marzia Varettoni Simone Ferrero Daniela Drandi |
| author_sort | Martina Ferrante |
| collection | DOAJ |
| description | In IgM monoclonal gammopathies MYD88<sup>L265P</sup> is a prognostic and predictive biomarker of therapy response. MYD88<sup>L265P</sup> detection is mainly performed by allele-specific quantitative PCR (ASqPCR), however recently, droplet digital PCR (ddPCR) has been proved to be suitable for MYD88<sup>L265P</sup> screening and minimal residual disease monitoring (MRD). This study compared ASqPCR and ddPCR to define the most sensitive method for MYD88<sup>L265P</sup> detection in bone marrow (BM), peripheral blood (PB) sorted or unsorted CD19+ cells, and in plasma cell-free DNA (cfDNA). Overall, the analysis showed a good concordance rate (74%) between the two methods, especially in BM samples, while discordances (26%) were mostly in favor of ddPCR (ddPCR+ vs. ASqPCR-) and were particularly evident in samples with low mutational burden, such as PB and cfDNA. This study highlights ddPCR as a feasible approach for MYD88<sup>L265P</sup> detection across different specimen types (including cfDNA). Interestingly, its high sensitivity makes CD19+ selection dispensable. On the other hand, our results showed that MYD88<sup>L265P</sup> detection on PB samples, especially with ASqPCR, is suboptimal for screening and MRD analysis. Finally, significantly different MYD88<sup>L265P</sup> mutational levels observed between Waldenström Macroglobulinemia and IgM monoclonal gammopathy of undetermined significance patients suggest the need for further studies in order to identify possible correlations between mutational levels and risk of progression to Waldenström. |
| first_indexed | 2024-03-10T11:56:49Z |
| format | Article |
| id | doaj.art-371db568c5794271940665ed00da127b |
| institution | Directory Open Access Journal |
| issn | 2075-4418 |
| language | English |
| last_indexed | 2024-03-10T11:56:49Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Diagnostics |
| spelling | doaj.art-371db568c5794271940665ed00da127b2023-11-21T17:13:52ZengMDPI AGDiagnostics2075-44182021-04-0111577910.3390/diagnostics11050779MYD88<sup>L265P</sup> Detection in IgM Monoclonal Gammopathies: Methodological Considerations for Routine ImplementationMartina Ferrante0Daniela Furlan1Silvia Zibellini2Michela Borriero3Chiara Candido4Nora Sahnane5Silvia Uccella6Elisa Genuardi7Beatrice Alessandria8Benedetta Bianchi9Barbara Mora10Daniele Grimaldi11Irene Defrancesco12Cristina Jiménez13Federica Cavallo14Dario Ferrero15Irene Dogliotti16Michele Merli17Marzia Varettoni18Simone Ferrero19Daniela Drandi20Department of Molecular Biotechnology and Health Sciences, Hematology Division, University of Torino, 10100 Torino, ItalyDepartment of Medicine and Surgery, University of Insubria, 21100 Varese, ItalyDivision of Hematology, IRCCS Foundation, Policlinico San Matteo, 27100 Pavia, ItalyDepartment of Molecular Biotechnology and Health Sciences, Hematology Division, University of Torino, 10100 Torino, ItalyDivision of Hematology, IRCCS Foundation, Policlinico San Matteo, 27100 Pavia, ItalyUniversity Hospital “Ospedale di Circolo e Fondazione Macchi”-ASST Sette Laghi, University of Insubria, 21100 Varese, ItalyDepartment of Medicine and Surgery, University of Insubria, 21100 Varese, ItalyDepartment of Molecular Biotechnology and Health Sciences, Hematology Division, University of Torino, 10100 Torino, ItalyDepartment of Molecular Biotechnology and Health Sciences, Hematology Division, University of Torino, 10100 Torino, ItalyUniversity Hospital “Ospedale di Circolo e Fondazione Macchi”-ASST Sette Laghi, University of Insubria, 21100 Varese, ItalyUniversity Hospital “Ospedale di Circolo e Fondazione Macchi”-ASST Sette Laghi, University of Insubria, 21100 Varese, ItalyDepartment of Molecular Biotechnology and Health Sciences, Hematology Division, University of Torino, 10100 Torino, ItalyDivision of Hematology, IRCCS Foundation, Policlinico San Matteo, 27100 Pavia, ItalyHematology Department, University Hospital of Salamanca, Research Biomedical Institute of Salamanca (IBSAL), CIBERONC and Center for Cancer Research-IBMCC (USAL-CSIC), 37001 Salamanca, SpainDepartment of Molecular Biotechnology and Health Sciences, Hematology Division, University of Torino, 10100 Torino, ItalyDepartment of Molecular Biotechnology and Health Sciences, Hematology Division, University of Torino, 10100 Torino, ItalyStem Cell Transplant Unit, University Hospital AOU Città della Salute e della Scienza, 10100 Torino, ItalyUniversity Hospital “Ospedale di Circolo e Fondazione Macchi”-ASST Sette Laghi, University of Insubria, 21100 Varese, ItalyDivision of Hematology, IRCCS Foundation, Policlinico San Matteo, 27100 Pavia, ItalyDepartment of Molecular Biotechnology and Health Sciences, Hematology Division, University of Torino, 10100 Torino, ItalyDepartment of Molecular Biotechnology and Health Sciences, Hematology Division, University of Torino, 10100 Torino, ItalyIn IgM monoclonal gammopathies MYD88<sup>L265P</sup> is a prognostic and predictive biomarker of therapy response. MYD88<sup>L265P</sup> detection is mainly performed by allele-specific quantitative PCR (ASqPCR), however recently, droplet digital PCR (ddPCR) has been proved to be suitable for MYD88<sup>L265P</sup> screening and minimal residual disease monitoring (MRD). This study compared ASqPCR and ddPCR to define the most sensitive method for MYD88<sup>L265P</sup> detection in bone marrow (BM), peripheral blood (PB) sorted or unsorted CD19+ cells, and in plasma cell-free DNA (cfDNA). Overall, the analysis showed a good concordance rate (74%) between the two methods, especially in BM samples, while discordances (26%) were mostly in favor of ddPCR (ddPCR+ vs. ASqPCR-) and were particularly evident in samples with low mutational burden, such as PB and cfDNA. This study highlights ddPCR as a feasible approach for MYD88<sup>L265P</sup> detection across different specimen types (including cfDNA). Interestingly, its high sensitivity makes CD19+ selection dispensable. On the other hand, our results showed that MYD88<sup>L265P</sup> detection on PB samples, especially with ASqPCR, is suboptimal for screening and MRD analysis. Finally, significantly different MYD88<sup>L265P</sup> mutational levels observed between Waldenström Macroglobulinemia and IgM monoclonal gammopathy of undetermined significance patients suggest the need for further studies in order to identify possible correlations between mutational levels and risk of progression to Waldenström.https://www.mdpi.com/2075-4418/11/5/779ddPCRASqPCRMYD88WMIgM-MGUS |
| spellingShingle | Martina Ferrante Daniela Furlan Silvia Zibellini Michela Borriero Chiara Candido Nora Sahnane Silvia Uccella Elisa Genuardi Beatrice Alessandria Benedetta Bianchi Barbara Mora Daniele Grimaldi Irene Defrancesco Cristina Jiménez Federica Cavallo Dario Ferrero Irene Dogliotti Michele Merli Marzia Varettoni Simone Ferrero Daniela Drandi MYD88<sup>L265P</sup> Detection in IgM Monoclonal Gammopathies: Methodological Considerations for Routine Implementation Diagnostics ddPCR ASqPCR MYD88 WM IgM-MGUS |
| title | MYD88<sup>L265P</sup> Detection in IgM Monoclonal Gammopathies: Methodological Considerations for Routine Implementation |
| title_full | MYD88<sup>L265P</sup> Detection in IgM Monoclonal Gammopathies: Methodological Considerations for Routine Implementation |
| title_fullStr | MYD88<sup>L265P</sup> Detection in IgM Monoclonal Gammopathies: Methodological Considerations for Routine Implementation |
| title_full_unstemmed | MYD88<sup>L265P</sup> Detection in IgM Monoclonal Gammopathies: Methodological Considerations for Routine Implementation |
| title_short | MYD88<sup>L265P</sup> Detection in IgM Monoclonal Gammopathies: Methodological Considerations for Routine Implementation |
| title_sort | myd88 sup l265p sup detection in igm monoclonal gammopathies methodological considerations for routine implementation |
| topic | ddPCR ASqPCR MYD88 WM IgM-MGUS |
| url | https://www.mdpi.com/2075-4418/11/5/779 |
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