Childhood @entity981 is treated by combination chemotherapy with a number of drugs, almost always including the enzyme @entity4445 ( @entity4445 ). Although the initial remission rate is quite high, relapse and associated drug resistance remain a problem. In vitro studies have demonstrated an adaptive increase in @entity2734 synthetase (AS) expression in @entity4445 -resistant cells, which is believed to permit @entity4445 -resistant @entity1 @entity1778 cells to survive in vivo. The present results, obtained with @entity4445 -sensitive and -resistant @entity1 MOLT-4 @entity1778 cell lines, illustrate that several other adaptive processes occur to provide sufficient amounts of the AS substrates, @entity492 and @entity1160 , required to support this increased enzymic activity. In both cell populations, @entity492 is derived almost exclusively from intracellular sources, whereas the necessary @entity1160 arises from both intracellular and extracellular sources. Transport of @entity1160 into @entity4445 -resistant cells is significantly enhanced compared with the parental cells, whereas @entity535 efflux (e.g. @entity2734 ) is reduced. Most of the adaptive change for the @entity535 transporters, Systems A, ASC and L, is rapidly (12 h) reversed following @entity4445 removal. The enzymic activity of @entity1160 synthetase is also enhanced in @entity4445 -resistant cells by a post-transcriptional mechanism. The results demonstrate that there are several sites of metabolic adaptation in @entity4445 -treated @entity1778 cells that serve to promote the replenishment of both @entity1160 and @entity2734 .

Multiple adaptive mechanisms affect @entity2734 synthetase substrate availability in asparaginase-resistant MOLT-4 @entity1 XXXX cells.

@entity1 :: ('9606', 'Species') :: ['human'] @entity981 :: ('MESH:D054198', 'Disease') :: ['acute lymphoblastic leukaemia'] @entity1160 :: ('CHEBI:28300', 'Chemical') :: ['glutamine'] @entity535 :: ('CHEBI:33704', 'Chemical') :: ['amino acid'] @entity2734 :: ('CHEBI:17196', 'Chemical') :: ['asparagine'] @entity4445 :: ('80150', 'Gene') :: ['L-asparaginase', 'ASNase'] @entity1778 :: ('MESH:D007938', 'Disease') :: ['leukaemia'] @entity492 :: ('CHEBI:29995', 'Chemical') :: ['aspartate']
@entity1778 :: (MESH:D007938,Disease) :: ['leukaemia']
