The HPRT mutations in T lymphocytes are widely utilized as biomarkers of en
vironmental exposure and effect. The HPRT gene detects a wide variety of mu
tation types, many of which an similar at the molecular level to those foun
d in oncogenes in cancers. However, it remains to be determined whether the
assay for mutations in T lymphocytes is reflective of mutagenic events in
tissues or cells which have high frequencies of malignancy in humans. We no
w demonstrate that the HPRT gene can be utilized to detect mutations in mye
loid stem cells, which are frequent progenitor cells of leukemias. This mye
loid stem cell assay shows an age related increase in mutation at HPRT and
also detects increases in mutant frequency (M-MF) in patients who have unde
rgone chemotherapy. The myeloid mutants are confined to have mutations in t
he HPRT gene by DNA sequence analysis. Increases in M-MF are seen as expect
ed in the clonally unstable myeloid stem cells of patients with myelodyspla
stic syndromes; however, unexpectedly these patients also have elevated T-l
ymphocyte mutant frequencies (T-MF). A good correlation is shown between M-
MFs and T-MFs in the same patients. Thus, it appears that the T-lymphocyte
assay, which is technically much less demanding than the myeloid assay, app
ears to faithfully represent the frequency of mutagenic events in the myelo
id lineage. (C) 1999 Elsevier Science B.V. All rights reserved.