Purging in autologous hematopoietic stem cell transplantation using adenosine triphosphate (ATP) and 4-hydroperoxycyclophosphamide (4-HC)

Leukemia Research
Y HattaTakashi Horie

Abstract

In this study, we show potent in vitro purging induced by adenosine triphosphate (ATP) for leukemic cells. The treatment of murine L1210 leukemic cells with 2mM of ATP in vitro for 3h was able to reduce the number of leukemic clonogenic cells by about one order of magnitude presumably by changing the permeability of the leukemic cell membrane. Furthermore, the incubation of L1210 cells with ATP (2mM) and low dose 4-hydroperoxycyclophosphamide (4-HC, 2 microg/ml) for 3h resulted in at least a four-log reduction of clonogenic L1210 cells. Only a slight degree of toxicity to pluripotent hematopoietic stem cells (CFU-S) was observed in both treatment protocols. To determine the efficacy of pharmacological purging by ATP, we designed a murine system to mimic the conditions expected in the clinical setting of autologous transplantation using simulated partial remission marrow (SPRM) which was prepared by mixing normal marrow cells and L1210 cells at a ratio of 9:1. After the SPRM cells were incubated in vitro at a concentration of 1 x 10(6)/ml with both ATP (2mM) and low dose 4-HC (2 microg/ml) for 3h, 5 x 10(4) of the cells were then injected into lethally irradiated 9 weeks male BDF1 mice. All the mice given untreated-SPRM died of ...Continue Reading

References

Jan 1, 1991·The Journal of Cell Biology·L M ZhengJ D Young
Feb 1, 1986·Clinics in Haematology·G W Santos, O M Colvin
Apr 1, 1969·Journal of Cellular Physiology·H G HemplingG Gasic
Jul 7, 1981·Molecular and Cellular Biochemistry·R K Banerjee

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