Differentiation of promyelocytic leukaemia: alterations in Fas (CD95/Apo-1) and Fas ligand (CD178) expression.
The survival of leukaemic blasts contributes to the pathological mechanism of acute promyelocytic leukaemia (APL). While treatment of APL using retinoic acid (RA) is a model of differentiation therapy, little is known about possible effects of this treatment on the Fas/FasL system. Investigation of APL cells from patients undergoing differentiation therapy with RA and of promyelocytic HL-60 and monoblastic U-937 cells cultured with RA revealed a reduction of surface expression of both Fas and its ligand. Accordingly, the sensitivity of the cells to anti-Fas-induced apoptosis decreased proportionally and the reduced expression of FasL resulted in a decreased ability of the leukaemic cells to induce apoptosis in T cells. Our findings demonstrate that there are significant changes in Fas and FasL expression during RA treatment of APL, which probably have consequences for the interaction between host immune and leukaemia cells, and thus may be involved in the beneficial effects of differentiation therapy.
Salih
Helmut R
HR
Department of Immunology, Inflammation and Pulmonary Diseases, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, USA. Helmut.Salih@md.uni-tuebingen.de
Starling
Gary C
GC
Brandl
Stephan F
SF
Pelka-Fleischer
Renate
R
Haferlach
Torsten
T
Hiddemann
Wolfgang
W
Kiener
Peter A
PA
Nuessler
Volkmar
V
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects; D018920:Coculture Techniques; D053222:Fas Ligand Protein; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D019169:Jurkat Cells; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000032:analysis*; D014212:Tretinoin / Q000627:therapeutic use*; D020298:U937 Cells; D019014:fas Receptor / Q000032:analysis*
D000970:Antineoplastic Agents; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor; D014212:Tretinoin