Transcriptomic Analysis in Multiple Myeloma and Primary Plasma Cell Leukemia with t(11;14) Reveals Different Expression Patterns with Biological Implications in Venetoclax Sensitivity
Mechanisms underlying the pathophysiology of primary Plasma Cell Leukemia (pPCL) and intramedullary multiple myeloma (MM) need to be further elucidated, being potentially relevant for improving therapeutic approaches. In such a context, the MM and pPCL subgroups characterized by t(11;14) deserve a f...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
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MDPI AG
2021-09-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/19/4898 |
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| author | Katia Todoerti Elisa Taiana Noemi Puccio Vanessa Favasuli Marta Lionetti Ilaria Silvestris Massimo Gentile Pellegrino Musto Fortunato Morabito Umberto Gianelli Niccolò Bolli Luca Baldini Antonino Neri Domenica Ronchetti |
| author_facet | Katia Todoerti Elisa Taiana Noemi Puccio Vanessa Favasuli Marta Lionetti Ilaria Silvestris Massimo Gentile Pellegrino Musto Fortunato Morabito Umberto Gianelli Niccolò Bolli Luca Baldini Antonino Neri Domenica Ronchetti |
| author_sort | Katia Todoerti |
| collection | DOAJ |
| description | Mechanisms underlying the pathophysiology of primary Plasma Cell Leukemia (pPCL) and intramedullary multiple myeloma (MM) need to be further elucidated, being potentially relevant for improving therapeutic approaches. In such a context, the MM and pPCL subgroups characterized by t(11;14) deserve a focused investigation, as the presence of the translocation is mainly associated with sensitivity to venetoclax. Herein, we investigated a proprietary cohort of MM and pPCL patients, focusing on the transcriptional signature of samples carrying t(11;14), whose incidence increases in pPCL in association with an unfavorable outcome. In addition, we evaluated the expression levels of the BCL2-gene family members and of a panel of B-cell genes recently reported to be associated with sensitivity to venetoclax in MM. Moreover, transcriptional analysis of lncRNAs in the two clinical settings led to the identification of several differentially expressed transcripts, among which the SNGH6 deregulated lncRNA might be relevant in the pathogenesis and prognosis of pPCL with t(11;14). Overall, our data suggest that MMs and pPCLs with t(11;14) might be responsive to venetoclax based on different molecular programs, prompting further studies to elucidate better novel potential predictive biomarkers. |
| first_indexed | 2024-03-10T07:05:12Z |
| format | Article |
| id | doaj.art-d4888e8283024eaaab064e007a97baa3 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T07:05:12Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-d4888e8283024eaaab064e007a97baa32023-11-22T15:53:58ZengMDPI AGCancers2072-66942021-09-011319489810.3390/cancers13194898Transcriptomic Analysis in Multiple Myeloma and Primary Plasma Cell Leukemia with t(11;14) Reveals Different Expression Patterns with Biological Implications in Venetoclax SensitivityKatia Todoerti0Elisa Taiana1Noemi Puccio2Vanessa Favasuli3Marta Lionetti4Ilaria Silvestris5Massimo Gentile6Pellegrino Musto7Fortunato Morabito8Umberto Gianelli9Niccolò Bolli10Luca Baldini11Antonino Neri12Domenica Ronchetti13Department of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, ItalyDepartment of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, ItalyDepartment of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, ItalyDepartment of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, ItalyDepartment of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, ItalyDepartment of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, ItalyHematology Unit, “Annunziata” Hospital of Cosenza, 87100 Cosenza, ItalyDepartment of Emergency and Organ Transplantation, “Aldo Moro” University School of Medicine, 70124 Bari, ItalyHematology and Bone Marrow Transplant Unit, Hemato-Oncology Department, Augusta Victoria Hospital, East Jerusalem 91191, IsraelDepartment of Pathophysiology and Transplantation, University of Milan, 20122 Milan, ItalyDepartment of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, ItalyDepartment of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, ItalyDepartment of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, ItalyDepartment of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, ItalyMechanisms underlying the pathophysiology of primary Plasma Cell Leukemia (pPCL) and intramedullary multiple myeloma (MM) need to be further elucidated, being potentially relevant for improving therapeutic approaches. In such a context, the MM and pPCL subgroups characterized by t(11;14) deserve a focused investigation, as the presence of the translocation is mainly associated with sensitivity to venetoclax. Herein, we investigated a proprietary cohort of MM and pPCL patients, focusing on the transcriptional signature of samples carrying t(11;14), whose incidence increases in pPCL in association with an unfavorable outcome. In addition, we evaluated the expression levels of the BCL2-gene family members and of a panel of B-cell genes recently reported to be associated with sensitivity to venetoclax in MM. Moreover, transcriptional analysis of lncRNAs in the two clinical settings led to the identification of several differentially expressed transcripts, among which the SNGH6 deregulated lncRNA might be relevant in the pathogenesis and prognosis of pPCL with t(11;14). Overall, our data suggest that MMs and pPCLs with t(11;14) might be responsive to venetoclax based on different molecular programs, prompting further studies to elucidate better novel potential predictive biomarkers.https://www.mdpi.com/2072-6694/13/19/4898t(1114)multiple myelomaPlasma Cell LeukemiavenetoclaxlncRNA |
| spellingShingle | Katia Todoerti Elisa Taiana Noemi Puccio Vanessa Favasuli Marta Lionetti Ilaria Silvestris Massimo Gentile Pellegrino Musto Fortunato Morabito Umberto Gianelli Niccolò Bolli Luca Baldini Antonino Neri Domenica Ronchetti Transcriptomic Analysis in Multiple Myeloma and Primary Plasma Cell Leukemia with t(11;14) Reveals Different Expression Patterns with Biological Implications in Venetoclax Sensitivity Cancers t(11 14) multiple myeloma Plasma Cell Leukemia venetoclax lncRNA |
| title | Transcriptomic Analysis in Multiple Myeloma and Primary Plasma Cell Leukemia with t(11;14) Reveals Different Expression Patterns with Biological Implications in Venetoclax Sensitivity |
| title_full | Transcriptomic Analysis in Multiple Myeloma and Primary Plasma Cell Leukemia with t(11;14) Reveals Different Expression Patterns with Biological Implications in Venetoclax Sensitivity |
| title_fullStr | Transcriptomic Analysis in Multiple Myeloma and Primary Plasma Cell Leukemia with t(11;14) Reveals Different Expression Patterns with Biological Implications in Venetoclax Sensitivity |
| title_full_unstemmed | Transcriptomic Analysis in Multiple Myeloma and Primary Plasma Cell Leukemia with t(11;14) Reveals Different Expression Patterns with Biological Implications in Venetoclax Sensitivity |
| title_short | Transcriptomic Analysis in Multiple Myeloma and Primary Plasma Cell Leukemia with t(11;14) Reveals Different Expression Patterns with Biological Implications in Venetoclax Sensitivity |
| title_sort | transcriptomic analysis in multiple myeloma and primary plasma cell leukemia with t 11 14 reveals different expression patterns with biological implications in venetoclax sensitivity |
| topic | t(11 14) multiple myeloma Plasma Cell Leukemia venetoclax lncRNA |
| url | https://www.mdpi.com/2072-6694/13/19/4898 |
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