Targeting Chronic Myeloid Leukemia Stem/Progenitor Cells Using Venetoclax-Loaded Immunoliposome
CML is a hematopoietic stem-cell disorder emanating from breakpoint cluster region/Abelson murine leukemia 1 (BCR/ABL) translocation. Introduction of different TKIs revolutionized treatment outcome in CML patients, but CML LSCs seem insensitive to TKIs and are detectable in newly diagnosed and resis...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-03-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/6/1311 |
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| author | Mohammad Houshmand Francesca Garello Rachele Stefania Valentina Gaidano Alessandro Cignetti Michela Spinelli Carmen Fava Mahin Nikougoftar Zarif Sara Galimberti Ester Pungolino Mario Annunziata Luigia Luciano Giorgina Specchia Monica Bocchia Gianni Binotto Massimiliano Bonifacio Bruno Martino Patrizia Pregno Fabio Stagno Alessandra Iurlo Sabina Russo Silvio Aime Paola Circosta Giuseppe Saglio |
| author_facet | Mohammad Houshmand Francesca Garello Rachele Stefania Valentina Gaidano Alessandro Cignetti Michela Spinelli Carmen Fava Mahin Nikougoftar Zarif Sara Galimberti Ester Pungolino Mario Annunziata Luigia Luciano Giorgina Specchia Monica Bocchia Gianni Binotto Massimiliano Bonifacio Bruno Martino Patrizia Pregno Fabio Stagno Alessandra Iurlo Sabina Russo Silvio Aime Paola Circosta Giuseppe Saglio |
| author_sort | Mohammad Houshmand |
| collection | DOAJ |
| description | CML is a hematopoietic stem-cell disorder emanating from breakpoint cluster region/Abelson murine leukemia 1 (BCR/ABL) translocation. Introduction of different TKIs revolutionized treatment outcome in CML patients, but CML LSCs seem insensitive to TKIs and are detectable in newly diagnosed and resistant CML patients and in patients who discontinued therapy. It has been reported that CML LSCs aberrantly express some CD markers such as CD26 that can be used for the diagnosis and for targeting. In this study, we confirmed the presence of CD26+ CML LSCs in newly diagnosed and resistant CML patients. To selectively target CML LSCs/progenitor cells that express CD26 and to spare normal HSCs/progenitor cells, we designed a venetoclax-loaded immunoliposome (IL-VX). Our results showed that by using this system we could selectively target CD26+ cells while sparing CD26− cells. The efficiency of venetoclax in targeting CML LSCs has been reported and our system demonstrated a higher potency in cell death induction in comparison to free venetoclax. Meanwhile, treatment of patient samples with IL-VX significantly reduced CD26+ cells in both stem cells and progenitor cells population. In conclusion, this approach showed that selective elimination of CD26+ CML LSCs/progenitor cells can be obtained in vitro, which might allow in vivo reduction of side effects and attainment of treatment-free, long-lasting remission in CML patients. |
| first_indexed | 2024-03-10T13:13:10Z |
| format | Article |
| id | doaj.art-0a896ef93d264e3eb697531571e1d565 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T13:13:10Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-0a896ef93d264e3eb697531571e1d5652023-11-21T10:32:28ZengMDPI AGCancers2072-66942021-03-01136131110.3390/cancers13061311Targeting Chronic Myeloid Leukemia Stem/Progenitor Cells Using Venetoclax-Loaded ImmunoliposomeMohammad Houshmand0Francesca Garello1Rachele Stefania2Valentina Gaidano3Alessandro Cignetti4Michela Spinelli5Carmen Fava6Mahin Nikougoftar Zarif7Sara Galimberti8Ester Pungolino9Mario Annunziata10Luigia Luciano11Giorgina Specchia12Monica Bocchia13Gianni Binotto14Massimiliano Bonifacio15Bruno Martino16Patrizia Pregno17Fabio Stagno18Alessandra Iurlo19Sabina Russo20Silvio Aime21Paola Circosta22Giuseppe Saglio23Department of Clinical and Biological Sciences, University of Turin, 10043 Turin, ItalyMolecular and Preclinical Imaging Centres, Department of Molecular Biotechnology and Health Sciences, University of Turin, 10126 Turin, ItalyMolecular and Preclinical Imaging Centres, Department of Molecular Biotechnology and Health Sciences, University of Turin, 10126 Turin, ItalyDivision of Hematology, A.O. SS Antonio e Biagio e Cesare Arrigo, 15121 Alessandria, ItalyDepartment of Hematology and Cell Therapy, A.O. Ordine Mauriziano, 10128 Turin, ItalyADIENNE Pharma & Biotech SA, 6900 Lugano, SwitzerlandDepartment of Clinical and Biological Sciences, University of Turin, 10043 Turin, ItalyCenter for Hematology and Regenerative Medicine, Karolinska Institutet, Department of Medicine, Karolinska University Hospital Huddinge, 14186 Stockholm, SwedenDepartment of Hematology, Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, ItalyDivision of Hematology, ASST Grande Ospedale Metropolitano Niguarda, 20162 Milan, ItalyHematology Unit, Cardarelli Hospital, 80131 Naples, ItalyHematology Unit, Department of Clinical Medicine and Surgery, Federico II University, 80138 Naples, ItalySchool of Medicine, University of Bari ‘Aldo Moro’, 70121 Bari, ItalyHematology Unit, Department of Medicine, Surgery and Neuroscience, Azienda Ospedaliera Universitaria Senese, University of Siena, 53100 Siena, ItalyUnit of Hematology and Clinical Immunology, University of Padova, 35122 Padova, ItalyDepartment of Medicine, Section of Hematology, University of Verona, 37134 Verona, ItalyDivision of Hematology, Azienda Ospedaliera ‘Bianchi Melacrino Morelli’, 89124 Reggio Calabria, ItalyHematology Division, Oncology and Hematology Department, AOU Città della Salute e della Scienza di Torino, 10126 Turin, ItalyDivision of Hematology, Azienda Ospedaliero Universitaria Policlinico-Vittorio Emanuele Catania, 95124 Catania, ItalyIRCCS Ca’ Granda—Maggiore Policlinico Hospital Foundation, 20122 Milan, ItalyDivision of Hematology, University of Messina, 98100 Messina, ItalyMolecular and Preclinical Imaging Centres, Department of Molecular Biotechnology and Health Sciences, University of Turin, 10126 Turin, ItalyDepartment of Clinical and Biological Sciences, University of Turin, 10043 Turin, ItalyDepartment of Clinical and Biological Sciences, University of Turin, 10043 Turin, ItalyCML is a hematopoietic stem-cell disorder emanating from breakpoint cluster region/Abelson murine leukemia 1 (BCR/ABL) translocation. Introduction of different TKIs revolutionized treatment outcome in CML patients, but CML LSCs seem insensitive to TKIs and are detectable in newly diagnosed and resistant CML patients and in patients who discontinued therapy. It has been reported that CML LSCs aberrantly express some CD markers such as CD26 that can be used for the diagnosis and for targeting. In this study, we confirmed the presence of CD26+ CML LSCs in newly diagnosed and resistant CML patients. To selectively target CML LSCs/progenitor cells that express CD26 and to spare normal HSCs/progenitor cells, we designed a venetoclax-loaded immunoliposome (IL-VX). Our results showed that by using this system we could selectively target CD26+ cells while sparing CD26− cells. The efficiency of venetoclax in targeting CML LSCs has been reported and our system demonstrated a higher potency in cell death induction in comparison to free venetoclax. Meanwhile, treatment of patient samples with IL-VX significantly reduced CD26+ cells in both stem cells and progenitor cells population. In conclusion, this approach showed that selective elimination of CD26+ CML LSCs/progenitor cells can be obtained in vitro, which might allow in vivo reduction of side effects and attainment of treatment-free, long-lasting remission in CML patients.https://www.mdpi.com/2072-6694/13/6/1311chronic myeloid leukemialeukemia stem cellCD26liposomeimmunoliposometargeted therapy |
| spellingShingle | Mohammad Houshmand Francesca Garello Rachele Stefania Valentina Gaidano Alessandro Cignetti Michela Spinelli Carmen Fava Mahin Nikougoftar Zarif Sara Galimberti Ester Pungolino Mario Annunziata Luigia Luciano Giorgina Specchia Monica Bocchia Gianni Binotto Massimiliano Bonifacio Bruno Martino Patrizia Pregno Fabio Stagno Alessandra Iurlo Sabina Russo Silvio Aime Paola Circosta Giuseppe Saglio Targeting Chronic Myeloid Leukemia Stem/Progenitor Cells Using Venetoclax-Loaded Immunoliposome Cancers chronic myeloid leukemia leukemia stem cell CD26 liposome immunoliposome targeted therapy |
| title | Targeting Chronic Myeloid Leukemia Stem/Progenitor Cells Using Venetoclax-Loaded Immunoliposome |
| title_full | Targeting Chronic Myeloid Leukemia Stem/Progenitor Cells Using Venetoclax-Loaded Immunoliposome |
| title_fullStr | Targeting Chronic Myeloid Leukemia Stem/Progenitor Cells Using Venetoclax-Loaded Immunoliposome |
| title_full_unstemmed | Targeting Chronic Myeloid Leukemia Stem/Progenitor Cells Using Venetoclax-Loaded Immunoliposome |
| title_short | Targeting Chronic Myeloid Leukemia Stem/Progenitor Cells Using Venetoclax-Loaded Immunoliposome |
| title_sort | targeting chronic myeloid leukemia stem progenitor cells using venetoclax loaded immunoliposome |
| topic | chronic myeloid leukemia leukemia stem cell CD26 liposome immunoliposome targeted therapy |
| url | https://www.mdpi.com/2072-6694/13/6/1311 |
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