Predictive value of tyrosine phosphatase receptor gamma for the response to treatment tyrosine kinase inhibitors in chronic myeloid leukemia patients

Abstract Protein tyrosine phosphatase receptor gamma (PTPRG) is a member of the receptor-like family protein tyrosine phosphatases and acts as a tumor suppressor gene in different neoplasms. Recent studies reported the down-regulation of PTPRG expression levels in Chronic Myeloid Leukemia disease (C...

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Autores principales: Mohamed A. Ismail, Marzia Vezzalini, Hisham Morsi, Ahmad Abujaber, Ali Al Sayab, Kodappully Siveen, Mohamed A. Yassin, Maria Monne, Muthanna Samara, Richard Cook, Claudio Sorio, Helmout Modjtahedi, Nader I. Al-Dewik
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:6d88d7e906a945e29c80eab47db751fc2021-12-02T15:26:58ZPredictive value of tyrosine phosphatase receptor gamma for the response to treatment tyrosine kinase inhibitors in chronic myeloid leukemia patients10.1038/s41598-021-86875-y2045-2322https://doaj.org/article/6d88d7e906a945e29c80eab47db751fc2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86875-yhttps://doaj.org/toc/2045-2322Abstract Protein tyrosine phosphatase receptor gamma (PTPRG) is a member of the receptor-like family protein tyrosine phosphatases and acts as a tumor suppressor gene in different neoplasms. Recent studies reported the down-regulation of PTPRG expression levels in Chronic Myeloid Leukemia disease (CML). In addition, the BCR-ABL1 transcript level is currently a key predictive biomarker of CML response to treatment with Tyrosine Kinase Inhibitors (TKIs). The aim of this study was to employ flow cytometry to monitor the changes in the expression level of PTPRG in the white blood cells (WBCs) of CML patients at the time of diagnosis and following treatment with TKIs. WBCs from peripheral blood of 21 CML patients were extracted at diagnosis and during follow up along with seven healthy individuals. The PTPRG expression level was determined at protein and mRNA levels by both flow cytometry with monoclonal antibody (TPγ B9-2) and RT-qPCR, and BCR-ABL1 transcript by RT-qPCR, respectively. PTPRG expression was found to be lower in the neutrophils and monocytes of CML patients at time of diagnosis compared to healthy individuals. Treatment with TKIs nilotinib and Imatinib Mesylate restored the expression of PTPRG in the WBCs of CML patients to levels observed in healthy controls. Moreover, restoration levels were greatest in optimal responders and occurred earlier with nilotinib compared to imatinib. Our results support the measurement of PTPRG expression level in the WBCs of CML patients by flow cytometry as a monitoring tool for the response to treatment with TKIs in CML patients.Mohamed A. IsmailMarzia VezzaliniHisham MorsiAhmad AbujaberAli Al SayabKodappully SiveenMohamed A. YassinMaria MonneMuthanna SamaraRichard CookClaudio SorioHelmout ModjtahediNader I. Al-DewikNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Mohamed A. Ismail
Marzia Vezzalini
Hisham Morsi
Ahmad Abujaber
Ali Al Sayab
Kodappully Siveen
Mohamed A. Yassin
Maria Monne
Muthanna Samara
Richard Cook
Claudio Sorio
Helmout Modjtahedi
Nader I. Al-Dewik
Predictive value of tyrosine phosphatase receptor gamma for the response to treatment tyrosine kinase inhibitors in chronic myeloid leukemia patients
description Abstract Protein tyrosine phosphatase receptor gamma (PTPRG) is a member of the receptor-like family protein tyrosine phosphatases and acts as a tumor suppressor gene in different neoplasms. Recent studies reported the down-regulation of PTPRG expression levels in Chronic Myeloid Leukemia disease (CML). In addition, the BCR-ABL1 transcript level is currently a key predictive biomarker of CML response to treatment with Tyrosine Kinase Inhibitors (TKIs). The aim of this study was to employ flow cytometry to monitor the changes in the expression level of PTPRG in the white blood cells (WBCs) of CML patients at the time of diagnosis and following treatment with TKIs. WBCs from peripheral blood of 21 CML patients were extracted at diagnosis and during follow up along with seven healthy individuals. The PTPRG expression level was determined at protein and mRNA levels by both flow cytometry with monoclonal antibody (TPγ B9-2) and RT-qPCR, and BCR-ABL1 transcript by RT-qPCR, respectively. PTPRG expression was found to be lower in the neutrophils and monocytes of CML patients at time of diagnosis compared to healthy individuals. Treatment with TKIs nilotinib and Imatinib Mesylate restored the expression of PTPRG in the WBCs of CML patients to levels observed in healthy controls. Moreover, restoration levels were greatest in optimal responders and occurred earlier with nilotinib compared to imatinib. Our results support the measurement of PTPRG expression level in the WBCs of CML patients by flow cytometry as a monitoring tool for the response to treatment with TKIs in CML patients.
format article
author Mohamed A. Ismail
Marzia Vezzalini
Hisham Morsi
Ahmad Abujaber
Ali Al Sayab
Kodappully Siveen
Mohamed A. Yassin
Maria Monne
Muthanna Samara
Richard Cook
Claudio Sorio
Helmout Modjtahedi
Nader I. Al-Dewik
author_facet Mohamed A. Ismail
Marzia Vezzalini
Hisham Morsi
Ahmad Abujaber
Ali Al Sayab
Kodappully Siveen
Mohamed A. Yassin
Maria Monne
Muthanna Samara
Richard Cook
Claudio Sorio
Helmout Modjtahedi
Nader I. Al-Dewik
author_sort Mohamed A. Ismail
title Predictive value of tyrosine phosphatase receptor gamma for the response to treatment tyrosine kinase inhibitors in chronic myeloid leukemia patients
title_short Predictive value of tyrosine phosphatase receptor gamma for the response to treatment tyrosine kinase inhibitors in chronic myeloid leukemia patients
title_full Predictive value of tyrosine phosphatase receptor gamma for the response to treatment tyrosine kinase inhibitors in chronic myeloid leukemia patients
title_fullStr Predictive value of tyrosine phosphatase receptor gamma for the response to treatment tyrosine kinase inhibitors in chronic myeloid leukemia patients
title_full_unstemmed Predictive value of tyrosine phosphatase receptor gamma for the response to treatment tyrosine kinase inhibitors in chronic myeloid leukemia patients
title_sort predictive value of tyrosine phosphatase receptor gamma for the response to treatment tyrosine kinase inhibitors in chronic myeloid leukemia patients
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/6d88d7e906a945e29c80eab47db751fc
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