Asparaginase-induced asparagine deficiency is associated with antileukemic effects in animals and man. Amino acid requirements in vitro of fresh human leukemic cells were studied by means of uptake of uridine-3H, to seek other amino acids which might be critical for cellular integrity. Asparagine was unique in that addition of the amino acid resulted in distinct increase of uptake in both of two patients' acute lymphocytic leukemia cells to the level seen in 6C3HED mouse lymphoma. Asparagine requirement by other leukemic cells was inconsistent, and only four of 12 reached the level seen in acute lymphocytic leukemia. No other amino acid studied substituted for asparagine.

Omission of asparagine, however, did not lower the uptake to the levels seen upon omission of cysteine, glutamine, histidine, or tyrosine, in either acute lymphocytic or acute myelocytic leukemia. Since omission of serine, glycine, proline, or alanine had little influence on uridine uptake, they are unlikely targets for depression by enzymatic destruction or for competitive analog as a nutritional approach to chemotherapy. Depression of cysteine, glutamine histidine, or tyrosine, all considered to be nonessential amino acids for whole-animal nutrition, makes these amino acids reasonable targets for enzymatic destruction or chemotherapeutic antagonism because of their apparent initial role in leukemic cells in these short-term studies in vitro. Partial but consistent reduction of uptake by omission of arginine in acute myelocytic leukemia cells may also warrant further exploration.

1

This investigation was supported by USPHS Research Grant CA-5834 from the National Cancer Institute.

This content is only available via PDF.