Gene-expression profiling of systemic anaplastic large-cell lymphoma reveals differences based on ALK status and two distinct morphologic ALK+ subtypes.
With the use of microarray gene-expression profiling, we analyzed a homogeneous series of 32 patients with systemic anaplastic large-cell lymphoma (ALCL) and 5 ALCL cell lines. Unsupervised analysis classified ALCL in 2 clusters, corresponding essentially to morphologic subgroups (ie, common type vs small cell and "mixed" variants) and clinical variables. Patients with a morphologic variant of ALCL had advanced-stage disease. This group included a significant number of patients who experienced early relapse. Supervised analysis showed that ALK+ALCL and ALK- ALCL have different gene-expression profiles, further confirming that they are different entities. Among the most significantly differentially expressed genes between ALK+ and ALK- samples, we found BCL6, PTPN12, CEBPB, and SERPINA1 genes to be overexpressed in ALK+ ALCL. This result was confirmed at the protein level for BCL-6, C/EBPbeta and serpinA1 through tissue microarrays. The molecular signature of ALK- ALCL included overexpression of CCR7, CNTFR, IL22, and IL21 genes but did not provide any obvious clues to the molecular mechanism underlying this tumor subtype. Once confirmed on a larger number of patients, the results of the present study could be used for clinical and therapeutic management of patients at the time of diagnosis.
Lamant
Laurence
L
Institut National de la Santé et de la Recherche Médicale (INSERM) U563 Centre de physiopathologie Toulouse Purpan, Toulouse, France.
de Reyniès
Aurélien
A
Duplantier
Marie-Michèle
MM
Rickman
David S
DS
Sabourdy
Frédérique
F
Giuriato
Sylvie
S
Brugières
Laurence
L
Gaulard
Philippe
P
Espinos
Estelle
E
Delsol
Georges
G
D000077548:Anaplastic Lymphoma Kinase; D045744:Cell Line, Tumor; D048430:Cell Shape; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017728:Lymphoma, Large-Cell, Anaplastic / Q000145:classification / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases; D046888:Tissue Array Analysis
D012333:RNA, Messenger; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases