Document Detail

Differential gene expression in anaplastic lymphoma kinase-positive and anaplastic lymphoma kinase-negative anaplastic large cell lymphomas.
MedLine Citation:
PMID:  15948116     Owner:  NLM     Status:  MEDLINE    
Anaplastic large cell lymphoma (ALCL) is an aggressive large T- or null-cell lymphoma. Most ALCLs arising in children and young adults express a constitutively active receptor tyrosine kinase, anaplastic lymphoma kinase (ALK). Anaplastic large cell lymphomas lacking ALK are clinically heterogeneous and their pathogenesis is unknown. This study is the first complementary DNA (cDNA) microarray analysis using RNA extracted from tumor tissue (7 ALK+ ALCLs and 7 ALK- ALCLs) to identify genes differentially expressed or shared between the ALK+ and ALK- tumors. Unsupervised hierarchical clustering using the top 11 most statistically significant discriminator cDNAs correctly grouped all ALK+ and ALK- tumors. Hierarchical clustering analysis using the 44 cDNAs with the greatest differential expression between ALK+ and ALK- RNAs grouped 6 of 7 ALK+ ALCLs together and 1 ALK+ ALCL with the ALK- group. In general, ALK+ tumors overexpress genes encoding signal transduction molecules (SYK , LYN , CDC37) and underexpress transcription factor genes (including HOXC6 and HOX A3 ) compared with the ALK- group. Cyclin D3 was overexpressed in the ALK+ group and the cell cycle inhibitor p19INK4D was decreased in the ALK- group, suggesting different mechanisms of promoting G 1 /S transition. Both groups had similar proliferation rates. Genes highly expressed in both ALK- and ALK+ ALCLs included kinases (LCK, protein kinase C, vav2, and NKIAMRE) and antiapoptotic molecules, suggesting possible common pathogenetic mechanisms as well.
Mary Ann Thompson; Jennifer Stumph; Sarah E Henrickson; Andreas Rosenwald; Qifu Wang; Sandy Olson; Stephen J Brandt; Jeremy Roberts; Xueqiong Zhang; Yu Shyr; Marsha C Kinney
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Human pathology     Volume:  36     ISSN:  0046-8177     ISO Abbreviation:  Hum. Pathol.     Publication Date:  2005 May 
Date Detail:
Created Date:  2005-06-10     Completed Date:  2005-08-02     Revised Date:  2014-02-14    
Medline Journal Info:
Nlm Unique ID:  9421547     Medline TA:  Hum Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  494-504     Citation Subset:  IM    
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MeSH Terms
Aged, 80 and over
Cell Cycle Proteins / genetics,  metabolism
Cyclin D3
Cyclin-Dependent Kinase Inhibitor p19
Cyclins / genetics,  metabolism
Gene Expression*
Gene Expression Profiling
Lymphoma, Large B-Cell, Diffuse / enzymology*,  genetics*
Middle Aged
Oligonucleotide Array Sequence Analysis
Protein-Tyrosine Kinases / metabolism*
Receptor Protein-Tyrosine Kinases
Reverse Transcriptase Polymerase Chain Reaction
Grant Support
Reg. No./Substance:
0/CCND3 protein, human; 0/CDKN2D protein, human; 0/Cell Cycle Proteins; 0/Cyclin D3; 0/Cyclin-Dependent Kinase Inhibitor p19; 0/Cyclins; EC Kinases; EC Protein-Tyrosine Kinases; EC lymphoma kinase

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