[Experimental study on blocking immune escape of leukemia cells in the recipient after bone marrow transplantation].
OBJECTIVE
To investigate whether murine soluble Fas gene transfected marrow graft could block the immune escape of leukemia cells, so as to eliminate the residual leukemia cells and reduce relapse after bone marrow transplantation (BMT).


METHODS
The murine leukemia/lymphoma models were established by inoculating female C57BL/6 mice (H-2b) with 10(5) EL4 cells/mouse through caudal vein. Donors of BM grafts were C57BL/6 male mice. Bone marrow mononuclear cells (BMMCs) were transfected with sFas or EGFP by adenovirus (adsFas or adEGFP) 24 hours before BMT (group D or E). The following three groups were set simultaneously: group A, no BMMCs transplanted; group B, BMMCs transplanted with no adenoviruses transfection; group C, EL4 cells transfusion only. Hematopoietic reconstitution, generation of leukemia/lymphoma and the survival rate were observed in all the groups after BMT.


RESULTS
The spleen indices examined 11 days after BMT were not obviously different among group B, D and E (P > 0.05), but in group A were significantly lower than those in the groups B, D, E (P < 0.01). The leukocyte and platelet counts on day 30 after BMT were recovered in group B and D, but were very low in group C and E. The Y-chromosomes appeared 2 months after BMT. Bone marrow pictures in group B and D were almost normal, but in group C and E had plenty of lymphoblast-like tumor cells. Tumors were obviously revealed in the mice of group C and E by histopathology examination, but did not in group B and D. The survival rate was 0 in group A, 100% in group B and D, 12.5% in group C and 6.25% in group E. Compared with that in group E, the survival was significantly increased in the sFas group (P < 0.01).


CONCLUSIONS
Graft transfected with sFas gene prolonged the post-BMT survival of leukemia/lymphoma mice. The transfection of sFas might block the effect of the immune escape of EL4 cells through FasL.
Hu
Zhong-bo
ZB
Institute of Hematology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Zhang
You-shan
YS
Li
Ai-xiang
AX
Liu
Ling-bo
LB
Zou
Ping
P
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology; D003131:Combined Modality Therapy; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D007942:Leukemia, Experimental / Q000276:immunology / Q000628:therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014161:Transduction, Genetic; D014162:Transfection; D014184:Transplantation, Homologous; D019139:Tumor Escape; D019014:fas Receptor / Q000235:genetics
D019014:fas Receptor