Downregulation of NPM-ALK by siRNA causes anaplastic large cell lymphoma cell growth inhibition and augments the anti cancer effects of chemotherapy in vitro

F. Y Y Hsu, Yi Zhao, W. French Anderson, Patrick Bruce Johnston

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

The fusion protein, nucleophosmin-anaplastic lymphoma kinase (NPM-ALK), results from the chromosome translocation t(2;5)(p23;q25) and is present in 50-70 percent of anaplastic large-cell lymphomas (ALCLs). NPM-ALK is a constitutively activated kinase that transforms cells through stimulating several mitogenic signaling pathways. To examine if the NPM-ALK is a potential therapeutic target in ALCL, we used siRNA to specifically downregulate the expression of the NPM-ALK in ALCL cell lines. In this report, we demonstrated viability loss in t(2;5)-positive ALCL cell lines, SUDHL-1 and Karpas 299 cells, but not in lymphoma cell lines without the chromosome translocation, Jurkat and Granta 519 cells. Further study demonstrated that the downregulation of NPM-ALK resulted in decreased cell proliferation and increased cell apoptosis. When used in combination with chemotherapeutic agents, such as doxorubicin, the inhibition of the NPM-ALK augments the chemosensitivity of the tumor cells. These results revealed the importance of continuous expression of NPM-ALK in maintaining the growth of ALCL cells. Our data also suggested that the repression of the fusion gene might be a potential novel therapeutic strategy for NPM-ALK positive ALCLs.

Original languageEnglish (US)
Pages (from-to)240-248
Number of pages9
JournalCancer Investigation
Volume25
Issue number4
DOIs
StatePublished - May 2007

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Anaplastic Large-Cell Lymphoma
Small Interfering RNA
Down-Regulation
Drug Therapy
Growth
Neoplasms
Cell Line
Chromosomes
nucleophosmin
anaplastic lymphoma kinase
In Vitro Techniques
Gene Fusion
Doxorubicin
Lymphoma
Phosphotransferases
Cell Proliferation
Apoptosis

Keywords

  • ALCL
  • Lymphoma
  • siRNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Downregulation of NPM-ALK by siRNA causes anaplastic large cell lymphoma cell growth inhibition and augments the anti cancer effects of chemotherapy in vitro. / Hsu, F. Y Y; Zhao, Yi; Anderson, W. French; Johnston, Patrick Bruce.

In: Cancer Investigation, Vol. 25, No. 4, 05.2007, p. 240-248.

Research output: Contribution to journalArticle

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