Expression and functional role of the p75 interleukin 2 receptor chain on leukemic hairy cells.
Hairy cell leukemia is a chronic lymphoproliferative disorder characterized by the expansion of neoplastic B-cells expressing the p55 chain of the interleukin 2 receptor (IL-2R) system that is recognized by anti-CD25 monoclonal antibodies (mAb) and binds interleukin 2 (IL-2) with low affinity. In the present study we investigated leukemic hairy cells (HC) for the presence of the p75 IL-2R chain which binds IL-2 with intermediate affinity and plays a crucial role in transducing the message to the cell. For this purpose, we tested highly enriched leukemic HC from six hairy cell leukemia patients for the presence of IL-2R transcripts and for the expression of the p55 and p75 IL-2R chains on their surface membrane by flow cytometry and immunoprecipitation analyses. The functional role of IL-2 in the regulation of HC proliferation was also investigated. Our results indicate that freshly isolated HC express detectable messages for both the p75 IL-2R and the p55 IL-2R. Flow cytometry analysis demonstrated detectable levels of p75 IL-2R on the HC from all patients tested. A mixture of two specific mAb was able to immunoprecipitate detectable amounts of p75 IL-2R from leukemic HC. When leukemic HC were cultured in the presence of several concentrations of IL-2 a low proliferative response was observed. Moreover, the IL-2-driven proliferation of HC was markedly inhibited by anti-p75 IL-2R mAb and to a lesser extent by anti-p55 IL-2R mAb. These findings provide direct evidence of the expression of different IL-2 receptors on leukemic HC and suggest that these molecules might play a role in leukemic cell growth.
Trentin
L
L
Department of Clinical Medicine, Padua University School of Medicine, Italy.
Zambello
R
R
Benati
C
C
Cassatella
M
M
Agostini
C
C
Bulian
P
P
Adami
F
F
Carra
G
G
Pizzolo
G
G
Semenzato
G
G
D000328:Adult; D000906:Antibodies; D002455:Cell Division / Q000502:physiology; D002462:Cell Membrane / Q000502:physiology / Q000648:ultrastructure; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D007943:Leukemia, Hairy Cell / Q000235:genetics / Q000473:pathology*; D046911:Macromolecular Substances; D008297:Male; D008875:Middle Aged; D011233:Precipitin Tests; D012333:RNA, Messenger / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D014158:Transcription, Genetic / Q000235:genetics; D014407:Tumor Cells, Cultured
D000906:Antibodies; D007376:Interleukin-2; D046911:Macromolecular Substances; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2