Document Detail

Aberrant expression of IL-22 receptor 1 and autocrine IL-22 stimulation contribute to tumorigenicity in ALK+ anaplastic large cell lymphoma.
MedLine Citation:
PMID:  18509351     Owner:  NLM     Status:  MEDLINE    
One of the characteristic features of anaplastic lymphoma kinase (ALK)(+), anaplastic large cell lymphoma (ALK(+)ALCL) is the constitutive activation of signal transducers and activators of transcription-3 (STAT3), a defect believed to be important for the pathogenesis of these tumors. In this report, we describe the existence of an autocrine stimulatory loop involving interleukin-22 (IL-22) that contributes to STAT3 activation and tumorigenicity of ALK(+)ALCL. The IL-22 receptor, a heterodimer composed of IL-22R1 and IL-10R2, was expressed in all ALK(+)ALCL cell lines and tumors examined. The expression of IL-22R1 in ALK(+)ALCL is aberrant, as this protein is absent in benign lymphocytes. Although ALK(+)ALCL cells produce endogenous IL-22, addition of recombinant IL-22 to ALK(+)ALCL cell lines significantly increased STAT3 activation, cell proliferation and colony formation in soft agar. Opposite biological effects were observed in cells treated with recombinant IL-22 binding protein (a naturally occurring IL-22 decoy) or IL-22-neutralizing antibody. Nucleophosmin (NPM)-ALK, the characteristic fusion gene oncoprotein expressed in ALK(+)ALCL, directly contributes to the aberrant expression of IL-22R1, as transfection of NPM-ALK in Jurkat cells-induced IL-22R1 expression and IL-22-mediated STAT3 activation. To conclude, for the first time, we demonstrate the importance of the IL-22 autocrine pathway in a lymphoid malignancy, and reveal yet another novel function of NPM-ALK.
J Dien Bard; P Gelebart; M Anand; H M Amin; R Lai
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-05-29
Journal Detail:
Title:  Leukemia     Volume:  22     ISSN:  1476-5551     ISO Abbreviation:  Leukemia     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-08-13     Completed Date:  2008-09-11     Revised Date:  2014-04-08    
Medline Journal Info:
Nlm Unique ID:  8704895     Medline TA:  Leukemia     Country:  England    
Other Details:
Languages:  eng     Pagination:  1595-603     Citation Subset:  IM    
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MeSH Terms
Base Sequence
DNA Primers
Enzyme-Linked Immunosorbent Assay
Interleukins / metabolism,  physiology*
Lymphoma, Large-Cell, Anaplastic / genetics,  pathology*
MAP Kinase Signaling System
Microscopy, Confocal
Microscopy, Fluorescence
RNA, Small Interfering
Receptors, Interleukin / genetics*
Reverse Transcriptase Polymerase Chain Reaction
STAT3 Transcription Factor / metabolism
Signal Transduction
Grant Support
Reg. No./Substance:
0/DNA Primers; 0/Interleukins; 0/RNA, Small Interfering; 0/Receptors, Interleukin; 0/STAT3 Transcription Factor; 0/interleukin-22; 0/interleukin-22 receptor

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