A new monoclonal antibody detects downregulation of protein tyrosine phosphatase receptor type γ in chronic myeloid leukemia patients
Abstract Background Protein tyrosine phosphatase receptor gamma (PTPRG) is a ubiquitously expressed member of the protein tyrosine phosphatase family known to act as a tumor suppressor gene in many different neoplasms with mechanisms of inactivation including mutations and methylation of CpG islands...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2017-06-01
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| Series: | Journal of Hematology & Oncology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13045-017-0494-z |
| _version_ | 1819181608891056128 |
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| author | Marzia Vezzalini Andrea Mafficini Luisa Tomasello Erika Lorenzetto Elisabetta Moratti Zeno Fiorini Tessa L. Holyoake Francesca Pellicano Mauro Krampera Cristina Tecchio Mohamed Yassin Nader Al-Dewik Mohamed A. Ismail Ali Al Sayab Maria Monne Claudio Sorio |
| author_facet | Marzia Vezzalini Andrea Mafficini Luisa Tomasello Erika Lorenzetto Elisabetta Moratti Zeno Fiorini Tessa L. Holyoake Francesca Pellicano Mauro Krampera Cristina Tecchio Mohamed Yassin Nader Al-Dewik Mohamed A. Ismail Ali Al Sayab Maria Monne Claudio Sorio |
| author_sort | Marzia Vezzalini |
| collection | DOAJ |
| description | Abstract Background Protein tyrosine phosphatase receptor gamma (PTPRG) is a ubiquitously expressed member of the protein tyrosine phosphatase family known to act as a tumor suppressor gene in many different neoplasms with mechanisms of inactivation including mutations and methylation of CpG islands in the promoter region. Although a critical role in human hematopoiesis and an oncosuppressor role in chronic myeloid leukemia (CML) have been reported, only one polyclonal antibody (named chPTPRG) has been described as capable of recognizing the native antigen of this phosphatase by flow cytometry. Protein biomarkers of CML have not yet found applications in the clinic, and in this study, we have analyzed a group of newly diagnosed CML patients before and after treatment. The aim of this work was to characterize and exploit a newly developed murine monoclonal antibody specific for the PTPRG extracellular domain (named TPγ B9-2) to better define PTPRG protein downregulation in CML patients. Methods TPγ B9-2 specifically recognizes PTPRG (both human and murine) by flow cytometry, western blotting, immunoprecipitation, and immunohistochemistry. Results Co-localization experiments performed with both anti-PTPRG antibodies identified the presence of isoforms and confirmed protein downregulation at diagnosis in the Philadelphia-positive myeloid lineage (including CD34+/CD38bright/dim cells). After effective tyrosine kinase inhibitor (TKI) treatment, its expression recovered in tandem with the return of Philadelphia-negative hematopoiesis. Of note, PTPRG mRNA levels remain unchanged in tyrosine kinase inhibitors (TKI) non-responder patients, confirming that downregulation selectively occurs in primary CML cells. Conclusions The availability of this unique antibody permits its evaluation for clinical application including the support for diagnosis and follow-up of these disorders. Evaluation of PTPRG as a potential therapeutic target is also facilitated by the availability of a specific reagent capable to specifically detect its target in various experimental conditions. |
| first_indexed | 2024-12-22T22:32:57Z |
| format | Article |
| id | doaj.art-8e1412223b5b4e8fa36d87cc9b36e25b |
| institution | Directory Open Access Journal |
| issn | 1756-8722 |
| language | English |
| last_indexed | 2024-12-22T22:32:57Z |
| publishDate | 2017-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Hematology & Oncology |
| spelling | doaj.art-8e1412223b5b4e8fa36d87cc9b36e25b2022-12-21T18:10:23ZengBMCJournal of Hematology & Oncology1756-87222017-06-0110111110.1186/s13045-017-0494-zA new monoclonal antibody detects downregulation of protein tyrosine phosphatase receptor type γ in chronic myeloid leukemia patientsMarzia Vezzalini0Andrea Mafficini1Luisa Tomasello2Erika Lorenzetto3Elisabetta Moratti4Zeno Fiorini5Tessa L. Holyoake6Francesca Pellicano7Mauro Krampera8Cristina Tecchio9Mohamed Yassin10Nader Al-Dewik11Mohamed A. Ismail12Ali Al Sayab13Maria Monne14Claudio Sorio15Department of Medicine, University of VeronaDepartment of Medicine, University of VeronaDepartment of Medicine, University of VeronaSection of Physiology, Department of Neurological, Neuropsychological, Morphological and Motor Sciences, University of VeronaDepartment of Medicine, University of VeronaDepartment of Medicine, University of VeronaPaul O’Gorman Leukaemia Research Centre, College of Medical, Veterinary & Life Sciences, Institute of Cancer Sciences, University of GlasgowThe Beatson Institute for Cancer Research, Garscube EstateSection of Hematology, Department of Medicine, University of VeronaSection of Hematology, Department of Medicine, University of VeronaNational Center for Cancer Care and Research (NCCCR), Hamad Medical Corporation (HMC)Qatar Medical Genetics Center, Hamad Medical Corporation (HMC)Interim Translational Research Institute (iTRI), Hamad Medical CorporationNational Center for Cancer Care and Research (NCCCR), Hamad Medical Corporation (HMC)Centro di Diagnostica Biomolecolare e Citogenetica Emato-Oncologica, “San Francesco” HospitalDepartment of Medicine, University of VeronaAbstract Background Protein tyrosine phosphatase receptor gamma (PTPRG) is a ubiquitously expressed member of the protein tyrosine phosphatase family known to act as a tumor suppressor gene in many different neoplasms with mechanisms of inactivation including mutations and methylation of CpG islands in the promoter region. Although a critical role in human hematopoiesis and an oncosuppressor role in chronic myeloid leukemia (CML) have been reported, only one polyclonal antibody (named chPTPRG) has been described as capable of recognizing the native antigen of this phosphatase by flow cytometry. Protein biomarkers of CML have not yet found applications in the clinic, and in this study, we have analyzed a group of newly diagnosed CML patients before and after treatment. The aim of this work was to characterize and exploit a newly developed murine monoclonal antibody specific for the PTPRG extracellular domain (named TPγ B9-2) to better define PTPRG protein downregulation in CML patients. Methods TPγ B9-2 specifically recognizes PTPRG (both human and murine) by flow cytometry, western blotting, immunoprecipitation, and immunohistochemistry. Results Co-localization experiments performed with both anti-PTPRG antibodies identified the presence of isoforms and confirmed protein downregulation at diagnosis in the Philadelphia-positive myeloid lineage (including CD34+/CD38bright/dim cells). After effective tyrosine kinase inhibitor (TKI) treatment, its expression recovered in tandem with the return of Philadelphia-negative hematopoiesis. Of note, PTPRG mRNA levels remain unchanged in tyrosine kinase inhibitors (TKI) non-responder patients, confirming that downregulation selectively occurs in primary CML cells. Conclusions The availability of this unique antibody permits its evaluation for clinical application including the support for diagnosis and follow-up of these disorders. Evaluation of PTPRG as a potential therapeutic target is also facilitated by the availability of a specific reagent capable to specifically detect its target in various experimental conditions.http://link.springer.com/article/10.1186/s13045-017-0494-zMonoclonal antibodyProtein tyrosine phosphataseChronic myeloid leukemiaTumor suppressor geneBCR-ABL1 |
| spellingShingle | Marzia Vezzalini Andrea Mafficini Luisa Tomasello Erika Lorenzetto Elisabetta Moratti Zeno Fiorini Tessa L. Holyoake Francesca Pellicano Mauro Krampera Cristina Tecchio Mohamed Yassin Nader Al-Dewik Mohamed A. Ismail Ali Al Sayab Maria Monne Claudio Sorio A new monoclonal antibody detects downregulation of protein tyrosine phosphatase receptor type γ in chronic myeloid leukemia patients Journal of Hematology & Oncology Monoclonal antibody Protein tyrosine phosphatase Chronic myeloid leukemia Tumor suppressor gene BCR-ABL1 |
| title | A new monoclonal antibody detects downregulation of protein tyrosine phosphatase receptor type γ in chronic myeloid leukemia patients |
| title_full | A new monoclonal antibody detects downregulation of protein tyrosine phosphatase receptor type γ in chronic myeloid leukemia patients |
| title_fullStr | A new monoclonal antibody detects downregulation of protein tyrosine phosphatase receptor type γ in chronic myeloid leukemia patients |
| title_full_unstemmed | A new monoclonal antibody detects downregulation of protein tyrosine phosphatase receptor type γ in chronic myeloid leukemia patients |
| title_short | A new monoclonal antibody detects downregulation of protein tyrosine phosphatase receptor type γ in chronic myeloid leukemia patients |
| title_sort | new monoclonal antibody detects downregulation of protein tyrosine phosphatase receptor type γ in chronic myeloid leukemia patients |
| topic | Monoclonal antibody Protein tyrosine phosphatase Chronic myeloid leukemia Tumor suppressor gene BCR-ABL1 |
| url | http://link.springer.com/article/10.1186/s13045-017-0494-z |
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