Abstract:
:The purpose of this paper was to ascertain whether results obtained in cell cultures of AML clonogenic blast cells would provide a useful model for a clinical regimen that combines fludarabine (F-ara-AMP) and cytosine arabinoside (ara-C). In the cultures the nucleoside F-ara-A was used. Blast cells from the continuous lines OCI/AML-2 and OCI/AML-3 were grown, either in methylcellulose to quantify clonogenic cells, or in suspension to measure self-renewal as reflected in changes in numbers of clonogenic cells. F-ara-A, like ara-C, was found to be more toxic to blast stem cells in suspension than in the clonogenic assay, indicating that F-ara-A might, in addition to general cytotoxicity, have some specific inhibitory effects on self-renewing stem cells. F-ara-A was less cytotoxic than ara-C; but, when F-ara-A was given before ara-C, synergism was seen at some F-ara-A doses, as manifested by increased ara-C cytotoxicity. In contrast, when ara-C was given before F-ara-A, protection was observed. Control experiments make it unlikely that this effect is related to changes in the cell cycle following ara-C exposure. We conclude that the cellular studies reported here confirm previous pharmacological data indicating that F-ara-A before ara-C increases the effectiveness of ara-C by increasing the accumulation of ara-CTP. However the present experiments show that the synergism between F-ara-A and ara-C is dependent on both dose and schedule.
journal_name
Leukemiajournal_title
Leukemiaauthors
Rayappa C,McCulloch EAsubject
Has Abstractpub_date
1993-07-01 00:00:00pages
992-9issue
7eissn
0887-6924issn
1476-5551journal_volume
7pub_type
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