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Inhibition of ALK enzymatic activity in T-cell lymphoma cells induces apoptosis and suppresses proliferation and STAT3 phosphorylation independently of Jak3

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Standard

Inhibition of ALK enzymatic activity in T-cell lymphoma cells induces apoptosis and suppresses proliferation and STAT3 phosphorylation independently of Jak3. / Marzec, Michal; Kasprzycka, Monika; Ptasznik, Andrzej; Wlodarski, Pawel; Zhang, Qian; Ødum, Niels; Wasik, Mariusz A.

I: Laboratory Investigation, Bind 85, Nr. 12, 2005, s. 1544-54.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Marzec, M, Kasprzycka, M, Ptasznik, A, Wlodarski, P, Zhang, Q, Ødum, N & Wasik, MA 2005, 'Inhibition of ALK enzymatic activity in T-cell lymphoma cells induces apoptosis and suppresses proliferation and STAT3 phosphorylation independently of Jak3', Laboratory Investigation, bind 85, nr. 12, s. 1544-54. https://doi.org/10.1038/labinvest.3700348

APA

Marzec, M., Kasprzycka, M., Ptasznik, A., Wlodarski, P., Zhang, Q., Ødum, N., & Wasik, M. A. (2005). Inhibition of ALK enzymatic activity in T-cell lymphoma cells induces apoptosis and suppresses proliferation and STAT3 phosphorylation independently of Jak3. Laboratory Investigation, 85(12), 1544-54. https://doi.org/10.1038/labinvest.3700348

Vancouver

Marzec M, Kasprzycka M, Ptasznik A, Wlodarski P, Zhang Q, Ødum N o.a. Inhibition of ALK enzymatic activity in T-cell lymphoma cells induces apoptosis and suppresses proliferation and STAT3 phosphorylation independently of Jak3. Laboratory Investigation. 2005;85(12):1544-54. https://doi.org/10.1038/labinvest.3700348

Author

Marzec, Michal ; Kasprzycka, Monika ; Ptasznik, Andrzej ; Wlodarski, Pawel ; Zhang, Qian ; Ødum, Niels ; Wasik, Mariusz A. / Inhibition of ALK enzymatic activity in T-cell lymphoma cells induces apoptosis and suppresses proliferation and STAT3 phosphorylation independently of Jak3. I: Laboratory Investigation. 2005 ; Bind 85, Nr. 12. s. 1544-54.

Bibtex

@article{1ced1630fd0011ddb219000ea68e967b,
title = "Inhibition of ALK enzymatic activity in T-cell lymphoma cells induces apoptosis and suppresses proliferation and STAT3 phosphorylation independently of Jak3",
abstract = "Aberrant expression of the ALK tyrosine kinase as a chimeric protein with nucleophosmin (NPM) and other partners plays a key role in malignant cell transformation of T-lymphocytes and other cells. Here we report that two small-molecule, structurally related, quinazoline-type compounds, WHI-131 and WHI-154, directly inhibit enzymatic activity of NPM/ALK as demonstrated by in vitro kinase assays using a synthetic tyrosine-rich oligopeptide and the kinase itself as the substrates. The inhibition of NPM/ALK activity resulted in malignant T cells in suppression of their growth, induction of apoptosis and inhibition of tyrosine phosphorylation of STAT3, the key effector of the NPM/ALK-induced oncogenesis. We also show that the STAT3 tyrosine phosphorylation is mediated in the malignant T cells by NPM/ALK independently of Jak3 kinase as evidenced by the presence of STAT3 phosphorylation in the NPM/ALK-transfected BaF3 cells that do not express detectable Jak3 and in the NPM/ALK-positive malignant T cells with either Jak3 activity impaired by a pan-Jak or Jak3-selective inhibitor or Jak3 expression abrogated by Jak3 siRNA. The above results represent the 'proof-of-principle' experiments with regard to the ALK enzymatic activity as an attractive therapeutic target in T-cell lymphomas and other malignancies that express the kinase in an active form.",
author = "Michal Marzec and Monika Kasprzycka and Andrzej Ptasznik and Pawel Wlodarski and Qian Zhang and Niels {\O}dum and Wasik, {Mariusz A}",
note = "Keywords: Apoptosis; Blotting, Western; Cell Line, Tumor; Cell Proliferation; Dose-Response Relationship, Drug; Enzyme Inhibitors; Humans; Janus Kinase 3; Lymphoma, T-Cell; Phosphorylation; Protein-Tyrosine Kinases; Quinazolines; STAT3 Transcription Factor",
year = "2005",
doi = "10.1038/labinvest.3700348",
language = "English",
volume = "85",
pages = "1544--54",
journal = "Laboratory Investigation",
issn = "0023-6837",
publisher = "nature publishing group",
number = "12",

}

RIS

TY - JOUR

T1 - Inhibition of ALK enzymatic activity in T-cell lymphoma cells induces apoptosis and suppresses proliferation and STAT3 phosphorylation independently of Jak3

AU - Marzec, Michal

AU - Kasprzycka, Monika

AU - Ptasznik, Andrzej

AU - Wlodarski, Pawel

AU - Zhang, Qian

AU - Ødum, Niels

AU - Wasik, Mariusz A

N1 - Keywords: Apoptosis; Blotting, Western; Cell Line, Tumor; Cell Proliferation; Dose-Response Relationship, Drug; Enzyme Inhibitors; Humans; Janus Kinase 3; Lymphoma, T-Cell; Phosphorylation; Protein-Tyrosine Kinases; Quinazolines; STAT3 Transcription Factor

PY - 2005

Y1 - 2005

N2 - Aberrant expression of the ALK tyrosine kinase as a chimeric protein with nucleophosmin (NPM) and other partners plays a key role in malignant cell transformation of T-lymphocytes and other cells. Here we report that two small-molecule, structurally related, quinazoline-type compounds, WHI-131 and WHI-154, directly inhibit enzymatic activity of NPM/ALK as demonstrated by in vitro kinase assays using a synthetic tyrosine-rich oligopeptide and the kinase itself as the substrates. The inhibition of NPM/ALK activity resulted in malignant T cells in suppression of their growth, induction of apoptosis and inhibition of tyrosine phosphorylation of STAT3, the key effector of the NPM/ALK-induced oncogenesis. We also show that the STAT3 tyrosine phosphorylation is mediated in the malignant T cells by NPM/ALK independently of Jak3 kinase as evidenced by the presence of STAT3 phosphorylation in the NPM/ALK-transfected BaF3 cells that do not express detectable Jak3 and in the NPM/ALK-positive malignant T cells with either Jak3 activity impaired by a pan-Jak or Jak3-selective inhibitor or Jak3 expression abrogated by Jak3 siRNA. The above results represent the 'proof-of-principle' experiments with regard to the ALK enzymatic activity as an attractive therapeutic target in T-cell lymphomas and other malignancies that express the kinase in an active form.

AB - Aberrant expression of the ALK tyrosine kinase as a chimeric protein with nucleophosmin (NPM) and other partners plays a key role in malignant cell transformation of T-lymphocytes and other cells. Here we report that two small-molecule, structurally related, quinazoline-type compounds, WHI-131 and WHI-154, directly inhibit enzymatic activity of NPM/ALK as demonstrated by in vitro kinase assays using a synthetic tyrosine-rich oligopeptide and the kinase itself as the substrates. The inhibition of NPM/ALK activity resulted in malignant T cells in suppression of their growth, induction of apoptosis and inhibition of tyrosine phosphorylation of STAT3, the key effector of the NPM/ALK-induced oncogenesis. We also show that the STAT3 tyrosine phosphorylation is mediated in the malignant T cells by NPM/ALK independently of Jak3 kinase as evidenced by the presence of STAT3 phosphorylation in the NPM/ALK-transfected BaF3 cells that do not express detectable Jak3 and in the NPM/ALK-positive malignant T cells with either Jak3 activity impaired by a pan-Jak or Jak3-selective inhibitor or Jak3 expression abrogated by Jak3 siRNA. The above results represent the 'proof-of-principle' experiments with regard to the ALK enzymatic activity as an attractive therapeutic target in T-cell lymphomas and other malignancies that express the kinase in an active form.

U2 - 10.1038/labinvest.3700348

DO - 10.1038/labinvest.3700348

M3 - Journal article

C2 - 16170336

VL - 85

SP - 1544

EP - 1554

JO - Laboratory Investigation

JF - Laboratory Investigation

SN - 0023-6837

IS - 12

ER -

ID: 10616927