Purging leukemic cells from simulated human remission marrow with alkyl-lysophospholipid.
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.
Okamoto
S
S
Olson
A C
AC
Vogler
W R
WR
Winton
E F
EF
D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D004305:Dose-Response Relationship, Drug; D005615:Freezing; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000473:pathology*; D008246:Lysophospholipids; D010743:Phospholipids / Q000494:pharmacology* / Q000633:toxicity; D013997:Time Factors
D008246:Lysophospholipids; D010743:Phospholipids