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

• Autorzy: Gloc E. , Warszawski M. , Mlynarski W. , Stolarska M. , Hoser G. , Skorski T. , Blasiak J.
• Języki publikacji: EN

Abstrakty

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. We 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.

Słowa kluczowe

EN

amifostine; idarubicin; DNA repair; oncogenic tyrosine kinase; lymphoblastic leukemia; DNA damage; childhood; chromosomal translocation; T cell

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 2002
• Tom: 49
• Numer: 1
• Opis fizyczny: p.121-128,fig.

Twórcy

autor

Gloc E.

• University of Lodz, S.Banacha 12-16, 90-237 Lodz, Poland

autor

Warszawski M.

autor

Mlynarski W.

autor

Stolarska M.

autor

Hoser G.

autor

Skorski T.

autor

Blasiak J.

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