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Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2017

Open Access 01-12-2017 | Research

A new monoclonal antibody detects downregulation of protein tyrosine phosphatase receptor type γ in chronic myeloid leukemia patients

Authors: 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

Published in: Journal of Hematology & Oncology | Issue 1/2017

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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.
Appendix
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Metadata
Title
A new monoclonal antibody detects downregulation of protein tyrosine phosphatase receptor type γ in chronic myeloid leukemia patients
Authors
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
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2017
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-017-0494-z

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