title: The expression and oncogenic effects of the embryonic stem cell marker SALL4 in ALK-positive anaplastic large cell lymphoma.
abstract: 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.
authors: Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Canada.
authors: Peng
authors: P
authors: Wang
authors: Jing Dong
authors: JD
authors: Zhang
authors: Fang
authors: F
authors: Wu
authors: Xiaoxia
authors: X
authors: Ye
authors: David
authors: D
authors: Sharon
authors: Mary
authors: M
authors: Hitt
authors: Todd P
authors: TP
authors: McMullen
authors: Samar A
authors: SA
authors: Hegazy
authors: Pascal
authors: P
authors: Gelebart
authors: Jianchang
authors: J
authors: Yang
authors: Yupo
authors: Y
authors: Ma
authors: Raymond
authors: R
authors: Lai
mesh_terms: D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D020169:Caspases / Q000378:metabolism; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology; D017728:Lymphoma, Large-Cell, Anaplastic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; D034741:RNA, Small Interfering; C472575:SALL4 protein, human; D050796:STAT3 Transcription Factor; D014157:Transcription Factors; C107023:p80(NPM-ALK) protein; D011505:Protein-Tyrosine Kinases; D020169:Caspases