Serpin A1 is overexpressed in ALK+ anaplastic large cell lymphoma and its expression correlates with extranodal dissemination.
Anaplastic large cell lymphoma (ALCL) is a distinct subtype of non-Hodgkin's lymphoma. Most of ALCLs (85%) carry a chromosomal translocation involving different partners in the 5' portion, and the anaplastic lymphoma kinase (ALK) receptor kinase domain in the 3' portion. These translocations induce the ectopic expression of X-ALK proteins, thought to be involved in lymphomagenesis, through the dysregulation of cell proliferation and apoptotic pathways. In the present study, based on several ALK+ and ALK- ALCL cell lines and biopsy specimens, we showed that serpin A1, a secretory glycoprotein, was overexpressed in ALK+ ALCL cell lines and ALK+ tumors at both the transcriptional and translational levels. The crucial role of NPM-ALK in the regulation of serpin A1 expression was further demonstrated by using both ectopic expression and downregulation, by RNA interference, of the NPM-ALK oncogene. In addition, in ALK+ tumors, serpin A1 expression appeared to be correlated with the clinical status of the patients as the serpin A1 mRNA level was higher in patients presenting with extranodal dissemination. These data, together with the pattern of expression of serpin A1 we observed in ALK+ tumors, suggest that serpin A1 has an invasion-promoting effect in ALK+ ALCL.
Duplantier
M M
MM
Department of Oncogenesis and Signaling in Hematopoietic Cells, Inserm U-563, Centre de Physiopathologie de Toulouse-Purpan, Toulouse, France.
Lamant
L
L
Sabourdy
F
F
de Reynies
A
A
Delsol
G
G
Espinos
E
E
D000328:Adult; D000077548:Anaplastic Lymphoma Kinase; D001706:Biopsy; D045744:Cell Line, Tumor; D002648:Child; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D009361:Neoplasm Invasiveness; D014176:Protein Biosynthesis; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases; D014158:Transcription, Genetic; D014178:Translocation, Genetic; D000515:alpha 1-Antitrypsin / Q000235:genetics* / Q000378:metabolism
D012333:RNA, Messenger; C043392:SERPINA1 protein, human; D000515:alpha 1-Antitrypsin; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases