Abstrait

Role of of protein tyrosine phosphatase receptor type γ in chronic myeloid leukemia

Claudio Sorio

 Protein tyrosine phosphatase receptor gamma (PTPRG) is a ubiquitously expressed member of the protein tyrosine phosphatasefamily known to act as a tumor suppressor gene in many different neoplasms with mechanisms of inactivation includingmutations and methylation of CpG islands in the promoter region. We identified a critical role in human hematopoiesis anddescribe a role as oncosuppressor in chronic myeloid leukemia (CML). We have described PTPRG expression in various tissuesand recently developed a monoclonal antibody capable of recognizing the native antigen of this phosphatase by flow cytometry: weconfirmed PTPRG protein downregulation in CML patients at diagnosis in the Philadelphia-positive myeloid lineage (includingCD34+/ CD38bright/dim cells). After effective tyrosine kinase inhibitor (TKI) treatment, its expression recovered in tandem withthe 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. We have also identified anovel regulative loop involving CTNNB1 gene. The availability of this unique antibody permits its evaluation for clinical applicationincluding the support for diagnosis and follow-up of these disorders. Evaluation of the role of PTPRG in health and disease isfacilitated by the availability of a specific reagent capable to specifically detect its target in various experimental conditions.