Abstract
MTA is produced in eukaryotic cells during the synthesis of polyamines from decarboxylated S-adenosylmethlonine. The nucleoside is rapidly cleaved to adenine and methylthioribose-1-P by MTA phosphoryiase (MTAse). We have assigned the gene MTAP to chromosome 9pter->9q12 by enzymatic and electrophoretic analysis of somatic cell hybrids.
All normal tissues and non-malginant cell lines contain MTAse. However, several human leukemic cell lines are deficient in the enzyme, and 5 patients with acute lymphoblastic leukemia (ALL) have been shown thus far to lack MTAse in their malignant cells. Karyotypic abnormalities involving fragile site 9p21 occur in ALL with lymphomatous clinical features. One of 5 such patients studied prospectively lacked MTAse in her leukemic cells but not in normal blood cells at remission. No inactive enzyme protein has been detected by immunoadsorption among 7 leukemic lines tested. The MTAse deficient cell lines excrete MTA up to 0.32 nmol/hr/mg protein. In mice, the growth of MTAse deficient mutant lymphoma cells (but not MTAse positive wild type cells) causes plasma MTA to rise from undetectable levels to > 800 nM pre-terminally. Assay of plasma or urine MTA may thus prove useful to screen leukemic patients for MTAse deficient malignant cell clones.
Article PDF
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Carrara, C., Willis, E., Chilcote, R. et al. 5′-DEOXY–5′-METHYLTHIOADENOSINE (MTA) PHOSPHORYLASE DEFICIENCY IN LEUKEMIA: GENETICS AND BIOCHEMICAL ASPECTS: 28. Pediatr Res 19, 748 (1985). https://doi.org/10.1203/00006450-198507000-00048
Issue Date:
DOI: https://doi.org/10.1203/00006450-198507000-00048