TEL/JAK2 tyrosine kinase inhibits DNA repair in the presence of amifostine.

• Authors: Ewa Gloc , Mariusz Warszawski , Wojciech Młynarski , Małgorzata Stolarska , Grażyna Hoser , Tomasz Skorski , Janusz Błasiak
• Languages of publication: EN

Abstracts

EN

The TEL/JAK2 chromosomal translocation (t(9;12)(p24;p13)) is associated with T cell childhood acute lymphoblastic leukemia. The TEL/JAK2 fusion protein contains the JAK2 catalytic domain and the TEL-specific oligomerization domain. TEL-mediated oligomerization of the TEL/JAK2 proteins results in the constitutive activation of the tyrosine kinase activity. Leukemia cells expressing TEL/JAK2 tyrosine kinase become resistant to anti-neoplastic drugs. Amifostine is a pro-drug which can selectively protect normal tissues against the toxicity of anticancer drugs and radiation. investigated the effects of amifostine on idarubicin-induced DNA damage and repair in murine pro-B lymphoid BaF3 cells and BaF3-TEL/JAK2-transformed cells using alkaline single cell gel electrophoresis (comet assay). Idarubicin induced DNA damage in both cell types but amifostine reduced its extent in control non-transformed BaF3 cells and enhanced it in TEL/JAK2-transformed cells. The transformed cells did not show measurable DNA repair after exposure to amifostine and idarubicin, but cells treated only with idarubicin were able to recover within a 60-min incubation. Because TEL/JAK2-transformed cells can be considered as model cells for certain human leukemias and lymphomas we anticipate an enhancement of idarubicin cytotoxicity by amifostine in these diseases. Moreover, TEL/JAK2 tyrosine kinase might be involved in cellular response to DNA damage. Amifostine could promote apoptosis or lower the threshold for apoptosis induction dependent on TEL/JAK2 activation.

Keywords

EN

oncogenic tyrosine kinase; amifostine; DNA damage; idarubicin; comet assay; DNA repair; TEL/JAK2

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2002
• Volume: 49
• Issue: 1
• Pages: 121-128

Dates

published

2002

received

2001-09-10

revised

2002-01-03

accepted

2002-02-21

Contributors

author

Ewa Gloc

• Department of Molecular Genetics, University of Łódź, S. Banacha 12/16, 90-237 Łódź, Poland

author

Mariusz Warszawski

• Department of Molecular Genetics, University of Łódź, Łódź, Poland

author

Wojciech Młynarski

• Oncohaematology Unit, Clinic of Pediatrics, Institute of Pediatrics, Medical University of Łódź, Łódź, Poland

author

Małgorzata Stolarska

• Oncohaematology Unit, Clinic of Pediatrics, Institute of Pediatrics, Medical University of Łódź, Łódź, Poland

author

Grażyna Hoser

• Medical Center for Postgraduate Education, Warszawa, Poland

author

Tomasz Skorski

• Center for Biotechnology, College of Science and Technology, Temple University, 1900 N. 12th Street, Philadelphia, PA 19122, U.S.A.

author

Janusz Błasiak

• Department of Molecular Genetics, University of Łódź, S. Banacha 12/16, 90-237 Łódź, Poland

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