Cysteine auxotrophy of human leukemic lymphoblasts is associated with decreased amounts of intracellular cystathionase protein

A series of human lymphoblastoid cell lines derived from nonleukemic donors are known to be cysteine prototrophs (cys+), while several lymphoblastoid lines derived from leukemic donors are cysteine auxotrophs (cys-). We have tested representative cell lines of each type for their content of cystathionase enzyme activity by a specific catalytic assay and their total cystathionase protein content by immunoprecipitation of in vivo labeled protein. There was a close correlation between the cellular content of the enzyme as determined in the two assays. Specifically, those cys+ lines having readily measureable enzyme by catalytic assay were found to contain significantly higher levels of immunoprecipitable Mr 43 000 cystathionase subunit than those cys- lines tested which were depleted in active enzyme. Thus, the absolute cysteine requirement of the leukemic, cys- cell lines tested is likely due to an intracellular reduction of cystathionase protein.