Experimental studies on the role of alkyl lysophospholipids in autologous bone marrow transplatation

William R. Vogler, Anita C. Olson, Shinichiro Okamoto, Lewis B. Somberg, Lewis Glasser

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

The selective cytocidal effect of alkyl lysophospholipids against neoplastic cells while sparing normal cells make these ideal candidates for purging leukemic cells from bone marrows obtained during remission. To test the feasibility of such an approach, a murine model and an in vitro human cell model were developed. In the murine system a mixture of normal bone marrow cells and WEHI IIIB myelomonocytic leukemic cells was incubated with varying doses of 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET-Me) for 24 hr before being injected into tail veins of lethally irradiated Balb/c mice. At doses of 20 and 100 μg/ml, long-term survivors were noted. The additional steps of freezing and thawing following incubation resulted in significantly longer survival with doses of 10 to 50 μg/ml, but were toxic to marrow stem cells at 100 μg/ml. In the in vitro model, normal marrow progenitor cells and leukemic cells (the promyelocytic cell line HL60) were exposed to varying concentrations of ET-Me for 1 and 4 hr alone or mixed, and clonogenicity was assayed by colony formation in semisolid medium during 7-14 days' incubation. At doses up to 100 μg/ml exposed for 4 hr normal progenitor cells were spared and HL60 colonies eliminated. Other phospholipids analogues were less effective in eliminating leukemic cells, but spared normal progenitor cells. A survey of fresh leukemic cells found varying degrees of sensitivity to ET-Me, indicating the need for testing a variety of compounds. These studies clearly indicated the potential usefulness of alkyl lysophospholipid compounds in selectively purging leukemic cells from remission marrows for autologous bone marrow transplantation.

Original languageEnglish
Pages (from-to)919-924
Number of pages6
JournalLipids
Volume22
Issue number11
DOIs
Publication statusPublished - 1987 Nov 1
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Cell Biology

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