In:
Scandinavian Journal of Immunology, Wiley, Vol. 39, No. 3 ( 1994-03), p. 327-332
Abstract:
Patients with homozygous deficiency of purine nucleoside phosphorylase (PNP) present with a T‐cell selective immune deficiency. To elucidate the potential use of PNP inhibitors in the therapy of cutaneous T‐cell lymphomas (CTCLs) the authors studied the effects of CI‐1000 (formerly PD 141955‐2) and CI‐972 on a T‐cell line My La established from a patient with mycosis fungoides. Both PNP inhibitors had significant, dose‐dependent, inhibitory effects on the proliferation of the T‐cell line. CI‐1000 (ED 50 : 3.7 μM) was approximately six‐fold more potent in blocking 3 H‐thymidine uptake than CI‐972 (ED 50 : 22.5 μM). The inhibitory effect of either substance could not be increased by addition of deoxyguanosine. Flow cytometric analysis revealed that both PNP inhibitors caused a block in the S‐phase of the cell cycle. The inhibitory effect on proliferation was reversible partially by addition of IL‐2. When testing proliferation inhibition of both substances on an IL‐2‐dependent T‐cell line (SeAx), their inhibitory effects were reduced significantly. These data document a mechanism of action of the PNP inhibitors independent of deoxyguanosine and partially reversible by IL‐2. The authors' observations suggest the potential use of PNP inhibitors in the therapy of cutaneous T‐cell lymphomas and provide evidence for a pathway independent from deoxyguanosine by which PNP inhibitors might function in T cells.
Type of Medium:
Online Resource
ISSN:
0300-9475
,
1365-3083
DOI:
10.1111/sji.1994.39.issue-3
DOI:
10.1111/j.1365-3083.1994.tb03379.x
Language:
English
Publisher:
Wiley
Publication Date:
1994
detail.hit.zdb_id:
2020954-X
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