Polyclonal rabbit antithymocyte globulin induces apoptosis and has cytotoxic effects on human leukemic cells.
The possibility of antileukemic activity of antithymocyte globulin (ATG) was investigated in 8 human leukemic cell lines and primary leukemic cells from 15 leukemia patients. The study demonstrated that ATG induced apoptosis and reduced proliferation in both cell lines and primary leukemic cells, particularly in lymphatic origin cells, indicating that ATG has broad-spectrum antileukemic activity, especially for cells of lymphatic origin.


BACKGROUND
Polyclonal ATGs are currently used to prevent graft-versus-host disease in allogeneic stem cell transplantation patients and to treat patients with severe aplastic anemia. It contains antibodies against antigens expressed on various hematopoietic cells, we hypothesized that it induces cell death not only in healthy cells but also in malignant hematopoietic cells.


METHODS
In this study, several human leukemic cell lines and primary leukemic cells from 15 patients with leukemia were used to investigate the ability of polyclonal ATGs to induce apoptosis and proliferation.


RESULTS
Polyclonal ATGs induced cell apoptosis in primary leukemic cells and in cell lines in a dose-dependent manner, and induced apoptosis in different populations through a variety of targets. Cell proliferation was significantly reduced in the presence of polyclonal ATGs; it arrested cells in the G0-G1 phase by cell cycle analysis. Treatment with polyclonal ATGs plus complement increased cytolysis of the leukemic cells; complement augments polyclonal ATG-induced leukemic cell death.


CONCLUSIONS
These data show that polyclonal ATG has broad-spectrum antileukemic activity, especially for cells of lymphatic origin, as it induced cell death through a variety of targets. This study provides an experimental basis for the application of polyclonal ATGs in allogeneic hematopoietic stem cell transplantation and in patients with lymphatic leukemia.
Department of Hematology, Shanghai Jiaotong University affiliated with The First People Hospital, Shanghai, China.
Huixia
H
Liu
Youwen
Y
Qin
Xiaorui
X
Wang
Kuangcheng
K
Xie
Yining
Y
Yang
Jun
J
Zhu
Chuxian
C
Zhao
Chun
C
Wang
D000818:Animals; D000906:Antibodies / Q000276:immunology; D000961:Antilymphocyte Serum / Q000276:immunology / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000276:immunology; D016923:Cell Death / Q000187:drug effects* / Q000276:immunology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016193:G1 Phase / Q000187:drug effects / Q000276:immunology; D018922:HL-60 Cells; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D019169:Jurkat Cells; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000601:surgery; D011817:Rabbits; D016192:Resting Phase, Cell Cycle / Q000187:drug effects / Q000276:immunology; D020298:U937 Cells
D000906:Antibodies; D000961:Antilymphocyte Serum