4.6 Article

The expression and oncogenic effects of the embryonic stem cell marker SALL4 in ALK-positive anaplastic large cell lymphoma

Journal

CELLULAR SIGNALLING
Volume 24, Issue 10, Pages 1955-1963

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2012.06.005

Keywords

SALL4; Embryonic stem cell marker; NPM-ALK; Anaplastic large cell lymphoma; Tumorigenecity

Categories

Ask authors/readers for more resources

SALL4 is one of the master transcriptional factors that are crucial in maintaining the pluripotency of embryonic stem cells (ESCs). While the expression of SALL4 is normally restricted to ESCs and somatic stem cells, we found that it is aberrantly expressed in ALK-positive anaplastic large cell lymphoma (ALK+ ALCL), a type of lymphoid malignancy carrying a mature T-cell immunophenotype. shRNA knockdown of SALL4 in ALK+ ALCL cell lines resulted in apoptosis and cell-cycle arrest, and significantly decreased colony formation on soft agar. These changes correlated with the downregulation of several anti-apoptotic proteins and facilitators of cell-cycle progression. Based on the differential response to a SALL4 reporter construct, we were able to separate two distinct cell subsets in Karpas 299 (an ALK+ ALCL cell line), namely SALL4(high) and SALL4(low). Importantly, the biological effects induced by SALL4 knock-down in Karpas 299 were restricted to the purified SALL4(high) cells, and this finding further supports the concept that SALL4 is biologically important in ALK+ ALCL Lastly, the expression of SALL4 was not dependent on the nucleophosmin (NPM)-anaplastic lymphoma kinase (ALK)/STAT3 signaling axis, the key oncogenic driver in ALK+ ALCL. To conclude, for the first time, our study has revealed the oncogenic contributions of an ESC protein in the pathogenesis of ALK+ ALCL. (C) 2012 Elsevier Inc. All rights reserved.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.6
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available