Expression and prognostic assessment of dipeptidyl peptidase IV and related enzymes in B-cell chronic lymphocytic leukemia.
Recent observations of the deregulated expression of several dipeptidyl peptidase (DP) IV-like enzymes in human cancers have led to presumptions of their pathogenic role in cancer. To further explore this concept we have characterized the expression of all DPIV-like enzymes in chronic lymphocytic leukemia (CLL). We have demonstrated the constitutive expression of DPIV, DP8, DP9, DPII and PEP mRNA and DPIV, DP8 and DP9 protein in CLL. FAP mRNA was not detected in CLL or normal B-lymphocytes. This correlated with an absence of FAP protein on the cell surface. This study also shows that DP8 mRNA expression is significantly upregulated in CLL compared to normal tonsil B-lymphocytes (p < 0.05) which may suggest biological importance in this disease. DP expression could not be correlated with any molecular or clinical prognostic markers for CLL in this cohort including IgVH mutational status, CD38, ZAP-70 or CD49d expression (n = 58). However, the constitutive expression of the DPIV-like enzymes in CLL and their emergence as potent immune regulators makes them candidate therapeutic targets in this disease.
School of Biological Sciences, Flinders University, Adelaide, SA, Australia.
Melanie L
ML
Sulda
Catherine A
CA
Abbott
Peter J
PJ
Macardle
Rachel K
RK
Hall
Bryone J
BJ
Kuss
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D004150:Dipeptidases / Q000235:genetics / Q000378:metabolism; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics / Q000378:metabolism*; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000235:genetics / Q000378:metabolism; D010450:Endopeptidases; D005260:Female; D018093:Gelatinases / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D050438:Genes, Immunoglobulin Heavy Chain / Q000235:genetics; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000201:enzymology* / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D000099167:Fibroblast Activation Protein Alpha
D014408:Biomarkers, Tumor; D004150:Dipeptidases; D018819:Dipeptidyl Peptidase 4; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D010450:Endopeptidases; D018093:Gelatinases; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D012697:Serine Endopeptidases; D000099167:Fibroblast Activation Protein Alpha; C514899:PREP protein, human; C471241:DPP9 protein, human; C100151:dipeptidyl peptidase II; C487997:DPP8 protein, human