trp mutation, which is found in the backbone of the DHFR molecule rather than in the active site, is currently under study. It is now important to carefully examine human neoplams to determine if alterations in DHFR lead to intrinsic or acquired drug resistance. The possibility that inherent or natural resistance of ANLL to MTX is due to the presence of an altered form of DHFR in blasts of untreated patients has been suggested by the observations of Dedhar et al.
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