Gene expression analysis of dendritic/Langerhans cells and Langerhans cell histiocytosis.
Langerhans cell histiocytosis (LCH) is a neoplastic disorder that results in clonal proliferation of cells with a Langerhans cell (LC) phenotype. The pathogenesis of LCH is still poorly understood. In the present study, serial analysis of gene expression (SAGE) was applied to LCs generated from umbilical cord blood CD34+ progenitor cells to identify LC-specific genes and the expression of these genes in LCH was investigated. Besides the expression of several genes known to be highly expressed in LCs and LCH such as CD1a, LYZ, and CD207, high expression of genes not previously reported to be expressed in LCs, such as GSN, MMP12, CCL17, and CCL22, was also identified. Further analysis of these genes by quantitative RT-PCR revealed high expression of FSCN1 and GSN in all 12 LCH cases analysed; of CD207, MMP12, CCL22, and CD1a in the majority of these cases; and CCL17 in three of the 12 cases. Immunohistochemistry confirmed protein expression in the majority of cases. The expression of MMP12 was most abundant in multi-system LCH, which is the LCH type with the worst prognosis. This suggests that expression of MMP12 may play a role in the progression of LCH. These data reveal new insight into the pathology of LCH and provide new starting points for further investigation of this clonal proliferative disorder.
Rust
R
R
Department of Pathology and Laboratory Medicine, University Medical Center Groningen and University of Groningen, The Netherlands.
Kluiver
J
J
Visser
L
L
Harms
G
G
Blokzijl
T
T
Kamps
W
W
Poppema
S
S
van den Berg
A
A
D015703:Antigens, CD / Q000032:analysis / Q000235:genetics; D018949:Antigens, CD1 / Q000032:analysis / Q000235:genetics; D015415:Biomarkers / Q000032:analysis; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D019742:Chemokines, CC / Q000032:analysis / Q000235:genetics; D018260:Gelsolin / Q000032:analysis / Q000235:genetics; D015870:Gene Expression; D020869:Gene Expression Profiling; D015723:Gene Library; D006646:Histiocytosis, Langerhans-Cell / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D016130:Immunophenotyping; D007801:Langerhans Cells / Q000737:chemistry*; D037181:Lectins, C-Type / Q000032:analysis / Q000235:genetics; D037241:Mannose-Binding Lectins / Q000032:analysis / Q000235:genetics; D053508:Matrix Metalloproteinase 12; D008666:Metalloendopeptidases / Q000032:analysis / Q000235:genetics; D008840:Microfilament Proteins / Q000032:analysis / Q000235:genetics; D009113:Muramidase / Q000032:analysis / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015703:Antigens, CD; D018949:Antigens, CD1; D015415:Biomarkers; C106230:CCL17 protein, human; C515482:CCL22 protein, human; C419393:CD1a antigen; C121916:CD207 protein, human; D002352:Carrier Proteins; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D019742:Chemokines, CC; D018260:Gelsolin; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D008840:Microfilament Proteins; C020324:fascin; D009113:Muramidase; D008666:Metalloendopeptidases; C507122:MMP12 protein, human; D053508:Matrix Metalloproteinase 12