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The X-chromosome linked gene encoding hypoxanthine phosphoribosyl transferase (HPRT) has been reported to provide a novel approach to the investigation of cell monoclonality in females based on non-random methylation-sensitive restriction enzyme cleavage of the active vs inactive HPRT alleles and a polymorphic Bam HI restriction site to distinguish the maternal and paternal gene copies. In a survey of 80 females, which included 65 cases of hemopoietic malignancy and 15 normal individuals, we found only nine (11.3%) to be heterozygous (informative) for the Bam HI polymorphism. Monoclonality was demonstrable by HPRT gene analysis in five of six informative cases of leukemia, the exception being a case of acute myeloid leukemia which displayed anomalous methylation of the HPRT gene. Our studies suggest that the applicability of the HPRT gene probe strategy may be limited by (1) the low frequency of informative cases and (2) potential inappropriate methylation of the HPRT gene in a proportion of cases.
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