Purging leukemic cells from simulated human remission marrow with alkyl-
lysophospholipid
S Okamoto, AC Olson, WR Vogler and EF Winton
Alkyl-lysophospholipids (ALP) are analogues of 2- lysophosphatidylcholine
that have been reported to have selective antitumor activity. These
compounds could potentially be useful in purging bone marrow of leukemic
cells in autologous marrow transplantation in acute leukemia. To determine
the efficacy of pharmacological purging by ALP, we have designed a human
assay system to mimic the conditions expected in the clinical setting of
autotransplantation using remission marrow. A simulated remission marrow
(SRM) was prepared by mixing normal marrow cells and HL60 cells in a ratio
of 1,000:1. The effect of cryopreservation on ALP-treated normal, HL60, and
SRM cells was examined. In separate experiments, ALP significantly reduced
the number of clonogenic HL60 cells with no effect on normal marrow
progenitors. The effect of ALP was more apparent after cryopreservation.
Incubation of HL60 cells with 50 micrograms/mL ALP for four hours followed
by cryopreservation resulted approximately in a 3 log reduction of
clonogenic HL60 cells. ALP also selectively purged the small number of
leukemic cells from SRM. In SRM, the data suggested that ALP had indirect
cytotoxic activity on leukemic cells by enhancing the cytotoxic activity of
monocytes in addition to its direct effect. We found no evidence that
clonogenic HL60 cells decreased because of induction of differentiation by
ALP. These data indicated that treatment of marrow cells with ALP offers an
efficient means to eliminate leukemic cells from the graft.
Volume 69,
Issue 5,
pp. 1381-1387,
05/01/1987
Copyright © 1987 by The American Society of Hematology
