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Protein Tyrosine Phosphatase Receptor Type γ Is a Functional Tumor Suppressor Gene Specifically Downregulated in Chronic Myeloid Leukemia  (2010)

Authors:
Della Peruta M.; Martinelli M.; Moratti E.; Pintani D.; Vezzalini M.; Mafficini A.; Grafone T.; Iacobucci I.; Soverini S.; Murineddu M.; Vinante F.; Tecchio C.; Piras G.; Gabbas A.; Monne M.; Sorio C.
Title:
Protein Tyrosine Phosphatase Receptor Type γ Is a Functional Tumor Suppressor Gene Specifically Downregulated in Chronic Myeloid Leukemia
Year:
2010
Type of item:
Articolo in Rivista
Tipologia ANVUR:
Articolo su rivista
Language:
Inglese
Format:
A Stampa
Referee:
Name of journal:
Cancer Research
ISSN of journal:
0008-5472
N° Volume:
70
Number or Folder:
21
Page numbers:
8896-8906
Keyword:
Chronic myeloid leukemia; tyrosine phosphatase; tumor suppressor gene; biomarker
Short description of contents:
Chronic myelogenous leukemia (CML) is the most common myeloproliferative disease. Protein tyrosine phosphatase receptor type γ (PTPRG) is a tumor suppressor gene and a myeloid cell marker expressed by CD34+ cells. Downregulation of PTPRG increases colony formation in the PTPRG-positive megakaryocytic cell lines MEG-01 and LAMA-84 but has no effect in the PTPRG-negative cell lines K562 and KYO-1. Its overexpression has an oncosuppressive effect in all these cell lines and is associated with myeloid differentiation and inhibition of BCR/ABL-dependent signaling. The intracellular domain of PTPRG directly interacts with BCR/ABL and CRKL, but not with signal transducers and activators of transcription 5. PTPRG is downregulated at the mRNA and protein levels in leukocytes of CML patients in both peripheral blood and bone marrow, including CD34+ cells, and is reexpressed following molecular remission of disease. Reexpression was associated to a loss of methylation of a CpG island of PTPRG promoter occurring in 55% of the patients analyzed. In K562 cell line, the DNA hypomethylating agent 5-aza-2′-deoxycytidine induced PTPRG expression and caused an inhibition of colony formation, partially reverted by downregulation of PTPRG expression. These findings establish, for the first time, PTPRG as a tumor suppressor gene involved in the pathogenesis of CML, suggesting its use as a potential diagnostic and therapeutic target.
Product ID:
57750
Handle IRIS:
11562/345316
Deposited On:
March 21, 2012
Last Modified:
January 31, 2019
Bibliographic citation:
Della Peruta M.; Martinelli M.; Moratti E.; Pintani D.; Vezzalini M.; Mafficini A.; Grafone T.; Iacobucci I.; Soverini S.; Murineddu M.; Vinante F.; Tecchio C.; Piras G.; Gabbas A.; Monne M.; Sorio C., Protein Tyrosine Phosphatase Receptor Type γ Is a Functional Tumor Suppressor Gene Specifically Downregulated in Chronic Myeloid Leukemia «Cancer Research» , vol. 70 , n. 212010pp. 8896-8906

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