In:
Acta Haematologica, S. Karger AG, Vol. 104, No. 2-3 ( 2000), p. 72-79
Abstract:
Lovastatin reduces the isoprenylation of p21 〈 sup 〉 ras 〈 /sup 〉 via suppression of mevalonic acid generation. Lovastatin has been shown to reduce tumor cell proliferation in a dose-dependent manner. Here, the potential of lovastatin for purging leukemia cells from bone marrow was investigated using the myeloblastic cell lines K562 and KG-1 as a model system, derived from an erythroleukemia and an acute myelogenous leukemia, respectively. Optimal purging conditions were determined using an MTT proliferation and a leukemia colony assay. Elimination of leukemia cells was time- and dose-dependent. Depletion of K562 was 2.5 logs for 100 μ 〈 i 〉 M 〈 /i 〉 of lovastatin at 72 h of incubation. Compared to another purging agent, 100 μg/ml mafosfamide had an activity comparable to 100 m 〈 i 〉 M 〈 /i 〉 lovastatin. Interestingly, KG-1 acute myelogenous leukemia cells were even more sensitive to lovastatin than K562 cells. In clonogenic assays, 100 μ 〈 i 〉 M 〈 /i 〉 of lovastatin resulted in a 3- to 4-log reduction of K562 colonies. Lovastatin had a progressive effect on normal hematopoietic progenitor cells. At a concentration of 100 μ 〈 i 〉 M 〈 /i 〉 of lovastatin, CFU-GM colonies were reduced by 1–2 logs. In conclusion, a differential effect on leukemia and normal progenitor cells could be detected in a clonogenic assay. These results suggest that lovastatin deserves further study as an agent for ex vivo marrow purging.
Type of Medium:
Online Resource
ISSN:
0001-5792
,
1421-9662
Language:
English
Publisher:
S. Karger AG
Publication Date:
2000
detail.hit.zdb_id:
1481888-7
detail.hit.zdb_id:
80008-9
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