Activity of tyrosine kinase inhibitors against human NUP214-ABL1-positive T cell malignancies

A. Quintás-Cardama, W. Tong, T. Manshouri, Francisco Vega, P. A. Lennon, J. Cools, D. G. Gilliland, F. Lee, J. Cortes, H. Kantarjian, G. Garcia-Manero

Research output: Contribution to journalArticle

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Abstract

Amplification of the NUP214-ABL1 oncogene can be detected in patients with T cell acute lymphoblastic leukemia (T-ALL). We screened 29 patients with T cell malignancies for the expression of NUP214-ABL1 by reverse transcription-polymerase chain reaction (RT-PCR). NUP214-ABL1 was detected in three (10%) patients. These results were confirmed by fluorescence in situ hybridization techniques. We also studied the activity of imatinib, nilotinib and dasatinib against the human NUP214-ABL1-positive cell lines PEER and BE-13. All three tyrosine kinase inhibitors decreased the viability of PEER and BE-13 cells, but nilotinib and dasatinib had >1-log lower IC50 values than imatinib (P <0.001). In contrast, the NUP214-ABL-negative T-ALL cell line Jurkat, was remarkably resistant to tyrosine kinase inhibition. The inhibition of cellular proliferation was associated with time-dependent induction of apoptosis and inhibition of ABL, CrKL and STAT5 phosphorylation. Moreover, dasatinib was active in a NUP214-ABL1-positive leukemia xenograft murine model and in marrow lymphoblasts from a patient with NUP214-ABL1-positive T-ALL. On the basis of these results, ABL1 kinase inhibitors warrant clinical investigation in patients with NUP214-ABL1-positive T-cell malignancies.

Original languageEnglish
Pages (from-to)1117-1124
Number of pages8
JournalLeukemia
Volume22
Issue number6
DOIs
StatePublished - Jun 1 2008
Externally publishedYes

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Protein-Tyrosine Kinases
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
T-Lymphocytes
Neoplasms
Cell Line
Fluorescence In Situ Hybridization
Oncogenes
Heterografts
Inhibitory Concentration 50
Reverse Transcription
Leukemia
Phosphotransferases
Bone Marrow
Phosphorylation
Cell Proliferation
Apoptosis
Polymerase Chain Reaction
Dasatinib
4-methyl-N-(3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-((4-pyridin-3-ylpyrimidin-2-yl)amino)benzamide
Imatinib Mesylate

ASJC Scopus subject areas

  • Hematology
  • Cancer Research

Cite this

Quintás-Cardama, A., Tong, W., Manshouri, T., Vega, F., Lennon, P. A., Cools, J., ... Garcia-Manero, G. (2008). Activity of tyrosine kinase inhibitors against human NUP214-ABL1-positive T cell malignancies. Leukemia, 22(6), 1117-1124. https://doi.org/10.1038/leu.2008.80

Activity of tyrosine kinase inhibitors against human NUP214-ABL1-positive T cell malignancies. / Quintás-Cardama, A.; Tong, W.; Manshouri, T.; Vega, Francisco; Lennon, P. A.; Cools, J.; Gilliland, D. G.; Lee, F.; Cortes, J.; Kantarjian, H.; Garcia-Manero, G.

In: Leukemia, Vol. 22, No. 6, 01.06.2008, p. 1117-1124.

Research output: Contribution to journalArticle

Quintás-Cardama, A, Tong, W, Manshouri, T, Vega, F, Lennon, PA, Cools, J, Gilliland, DG, Lee, F, Cortes, J, Kantarjian, H & Garcia-Manero, G 2008, 'Activity of tyrosine kinase inhibitors against human NUP214-ABL1-positive T cell malignancies', Leukemia, vol. 22, no. 6, pp. 1117-1124. https://doi.org/10.1038/leu.2008.80
Quintás-Cardama A, Tong W, Manshouri T, Vega F, Lennon PA, Cools J et al. Activity of tyrosine kinase inhibitors against human NUP214-ABL1-positive T cell malignancies. Leukemia. 2008 Jun 1;22(6):1117-1124. https://doi.org/10.1038/leu.2008.80
Quintás-Cardama, A. ; Tong, W. ; Manshouri, T. ; Vega, Francisco ; Lennon, P. A. ; Cools, J. ; Gilliland, D. G. ; Lee, F. ; Cortes, J. ; Kantarjian, H. ; Garcia-Manero, G. / Activity of tyrosine kinase inhibitors against human NUP214-ABL1-positive T cell malignancies. In: Leukemia. 2008 ; Vol. 22, No. 6. pp. 1117-1124.
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