A particular expression pattern of CD13 epitope 7H5 in chronic lymphocytic leukaemia--a possible new therapeutic target.
A total of 50 patients with chronic lymphocytic leukaemia (CLL), as well as the B-cell leukaemia cell lines MEC-1, JVM-3, and BV-173 were studied in order to assess the incidence of CD13/aminopeptidase N (APN) immunolabelling with a monoclonal antibody 7H5 compared to LeuM7 and to CD13 mRNA levels, and to correlate these data with the cytotoxic and apoptosis-induction activity of the natural phenolic APN inhibitor curcumin. CD13/APN was detected in a significant proportion of B-CLL patients (42/50, 84%), immunolabelled by 7H5 (42/50) ± LeuM7 (10/50). Molecular analysis for CD13 transcripts confirmed these data, resulting in a specific RT-PCR product in CD13 positive cases. Curcumin showed concentration-dependent cytoreductive efficacy and apoptosis-induction activity in all tested cell lines and primary cultures from CLL mononuclear cells. There was a clear tendency for a better response in CD13 positive cases. The incidence of CD13/APN in CLL suggests that the inhibition of APN/CD13 by curcumin may be an effective new molecular target for a more efficient therapy for these patients and warrants further investigations.
Laboratory of Haematopathology and Immunology, National Specialised Hospital for Active Treatment of Haematological Diseases, Sofia, Bulgaria. margenova@gmail.com
Margarita L
ML
Guenova
Antoaneta
A
Michova
Gueorgui N
GN
Balatzenko
Deyan Y
DY
Yosifov
Nikolay
N
Stoyanov
Hristo
H
Taskov
Martin R
MR
Berger
Spiro M
SM
Konstantinov
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D018826:CD13 Antigens / Q000037:antagonists & inhibitors / Q000235:genetics*; D045744:Cell Line, Tumor; D003474:Curcumin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D015448:Leukemia, B-Cell / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D061251:Primary Cell Culture; D012333:RNA, Messenger / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D012333:RNA, Messenger; D018826:CD13 Antigens; D003474:Curcumin