Pharmacologic marrow purging in murine T cell leukemia
EA Copelan, SC Johnson, MR Grever, JF Sheridan and PJ Tutschka
Ohio State University, Bone Marrow Transplantation Program, Columbus 43210.
Deoxycoformycin in combination with deoxyadenosine was used to purge 6C3HED
malignant T cells from murine marrow in vitro. Adenosine deaminase activity
of 6C3HED cells was ablated by incubation with 10(- 6) mol/L
deoxycoformycin (dCF). During a 12-hour incubation with 10(-6) mol/L dCF
and 10(-4) mol/L deoxyadenosine, tumor cells sequentially accumulated dATP,
became depleted of NAD followed by ATP, then died. More than 5 logs of
6C3HED cells were killed as measured by survival of mice injected with
treated tumor cells. Identical incubation of 5 x 10(6) marrow cells did not
interfere with rescue of syngeneic lethally irradiated mice. Long-term
survival was demonstrated in 12 of 14 mice that received marrow that had
been contaminated with 5% 6C3HED cells, incubated with deoxycoformycin and
deoxyadenosine, then used to rescue lethally irradiated mice. This murine
model provides information not available from in vitro assays and may be
useful in the development of strategies to purge malignant T cells from
marrow.
Volume 71,
Issue 6,
pp. 1656-1661,
06/01/1988
Copyright © 1988 by The American Society of Hematology
