Liquid biopsy-based monitoring of residual disease in multiple myeloma by analysis of the rearranged immunoglobulin genes-A feasibility study.
The need for sensitive monitoring of minimal/measurable residual disease (MRD) in multiple myeloma emerged as novel therapies led to deeper responses. Moreover, the potential benefits of blood-based analyses, the so-called liquid biopsy is prompting more and more studies to assess its feasibility. C...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2023-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0285696 |
| _version_ | 1797802042309214208 |
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| author | Anita Marx Magdolna Osváth Bence Szikora Orsolya Pipek István Csabai Ákos Nagy Csaba Bödör Zsolt Matula Ginette Nagy András Bors Ferenc Uher Gábor Mikala István Vályi-Nagy Imre Kacskovics |
| author_facet | Anita Marx Magdolna Osváth Bence Szikora Orsolya Pipek István Csabai Ákos Nagy Csaba Bödör Zsolt Matula Ginette Nagy András Bors Ferenc Uher Gábor Mikala István Vályi-Nagy Imre Kacskovics |
| author_sort | Anita Marx |
| collection | DOAJ |
| description | The need for sensitive monitoring of minimal/measurable residual disease (MRD) in multiple myeloma emerged as novel therapies led to deeper responses. Moreover, the potential benefits of blood-based analyses, the so-called liquid biopsy is prompting more and more studies to assess its feasibility. Considering these recent demands, we aimed to optimize a highly sensitive molecular system based on the rearranged immunoglobulin (Ig) genes to monitor MRD from peripheral blood. We analyzed a small group of myeloma patients with the high-risk t(4;14) translocation, using next-generation sequencing of Ig genes and droplet digital PCR of patient-specific Ig heavy chain (IgH) sequences. Moreover, well established monitoring methods such as multiparametric flow cytometry and RT-qPCR of the fusion transcript IgH::MMSET (IgH and multiple myeloma SET domain-containing protein) were utilized to evaluate the feasibility of these novel molecular tools. Serum measurements of M-protein and free light chains together with the clinical assessment by the treating physician served as routine clinical data. We found significant correlation between our molecular data and clinical parameters, using Spearman correlations. While the comparisons of the Ig-based methods and the other monitoring methods (flow cytometry, qPCR) were not statistically evaluable, we found common trends in their target detection. Regarding longitudinal disease monitoring, the applied methods yielded complementary information thus increasing the reliability of MRD evaluation. We also detected indications of early relapse before clinical signs, although this implication needs further verification in a larger patient cohort. |
| first_indexed | 2024-03-13T04:59:43Z |
| format | Article |
| id | doaj.art-72c26859dca34bd784adcddfb998a56a |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-03-13T04:59:43Z |
| publishDate | 2023-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-72c26859dca34bd784adcddfb998a56a2023-06-17T05:31:07ZengPublic Library of Science (PLoS)PLoS ONE1932-62032023-01-01185e028569610.1371/journal.pone.0285696Liquid biopsy-based monitoring of residual disease in multiple myeloma by analysis of the rearranged immunoglobulin genes-A feasibility study.Anita MarxMagdolna OsváthBence SzikoraOrsolya PipekIstván CsabaiÁkos NagyCsaba BödörZsolt MatulaGinette NagyAndrás BorsFerenc UherGábor MikalaIstván Vályi-NagyImre KacskovicsThe need for sensitive monitoring of minimal/measurable residual disease (MRD) in multiple myeloma emerged as novel therapies led to deeper responses. Moreover, the potential benefits of blood-based analyses, the so-called liquid biopsy is prompting more and more studies to assess its feasibility. Considering these recent demands, we aimed to optimize a highly sensitive molecular system based on the rearranged immunoglobulin (Ig) genes to monitor MRD from peripheral blood. We analyzed a small group of myeloma patients with the high-risk t(4;14) translocation, using next-generation sequencing of Ig genes and droplet digital PCR of patient-specific Ig heavy chain (IgH) sequences. Moreover, well established monitoring methods such as multiparametric flow cytometry and RT-qPCR of the fusion transcript IgH::MMSET (IgH and multiple myeloma SET domain-containing protein) were utilized to evaluate the feasibility of these novel molecular tools. Serum measurements of M-protein and free light chains together with the clinical assessment by the treating physician served as routine clinical data. We found significant correlation between our molecular data and clinical parameters, using Spearman correlations. While the comparisons of the Ig-based methods and the other monitoring methods (flow cytometry, qPCR) were not statistically evaluable, we found common trends in their target detection. Regarding longitudinal disease monitoring, the applied methods yielded complementary information thus increasing the reliability of MRD evaluation. We also detected indications of early relapse before clinical signs, although this implication needs further verification in a larger patient cohort.https://doi.org/10.1371/journal.pone.0285696 |
| spellingShingle | Anita Marx Magdolna Osváth Bence Szikora Orsolya Pipek István Csabai Ákos Nagy Csaba Bödör Zsolt Matula Ginette Nagy András Bors Ferenc Uher Gábor Mikala István Vályi-Nagy Imre Kacskovics Liquid biopsy-based monitoring of residual disease in multiple myeloma by analysis of the rearranged immunoglobulin genes-A feasibility study. PLoS ONE |
| title | Liquid biopsy-based monitoring of residual disease in multiple myeloma by analysis of the rearranged immunoglobulin genes-A feasibility study. |
| title_full | Liquid biopsy-based monitoring of residual disease in multiple myeloma by analysis of the rearranged immunoglobulin genes-A feasibility study. |
| title_fullStr | Liquid biopsy-based monitoring of residual disease in multiple myeloma by analysis of the rearranged immunoglobulin genes-A feasibility study. |
| title_full_unstemmed | Liquid biopsy-based monitoring of residual disease in multiple myeloma by analysis of the rearranged immunoglobulin genes-A feasibility study. |
| title_short | Liquid biopsy-based monitoring of residual disease in multiple myeloma by analysis of the rearranged immunoglobulin genes-A feasibility study. |
| title_sort | liquid biopsy based monitoring of residual disease in multiple myeloma by analysis of the rearranged immunoglobulin genes a feasibility study |
| url | https://doi.org/10.1371/journal.pone.0285696 |
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