Polyclonal rabbit antithymocyte globulin induces apoptosis and has cytotoxic effects on human leukemic cells.

Abstract

UNLABELLED:

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.

MATERIALS AND 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.

CONCLUSION:

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.

• Authors: Huixia Liu, Youwen Qin, Xiaorui Wang, Kuangcheng Xie, Yining Yang, Jun Zhu, Chuxian Zhao, Chun Wang
• Journal: Clinical lymphoma, myeloma & leukemia (Clin Lymphoma Myeloma Leuk) Vol. 12 Issue 5 Pg. 345-54 (Oct 2012) ISSN: 2152-2669 [Electronic] United States
• PMID: 22677206 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Antibodies
• Antilymphocyte Serum

Topics

• Animals
• Antibodies (immunology)
• Antilymphocyte Serum (immunology, pharmacology)
• Apoptosis (drug effects, immunology)
• Cell Cycle Checkpoints (drug effects, immunology)
• Cell Death (drug effects, immunology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• G1 Phase (drug effects, immunology)
• HL-60 Cells
• Hematopoietic Stem Cell Transplantation (methods)
• Humans
• Jurkat Cells
• K562 Cells
• Leukemia (drug therapy, immunology, pathology, surgery)
• Rabbits
• Resting Phase, Cell Cycle (drug effects, immunology)
• U937 Cells