HPRT mutations in vivo in human CD 34(+) hematopoietic stem cells

Citation
Bw. Grant et al., HPRT mutations in vivo in human CD 34(+) hematopoietic stem cells, MUT RES-F M, 431(2), 1999, pp. 183-198
Citations number
46
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
ISSN journal
1386-1964 → ACNP
Volume
431
Issue
2
Year of publication
1999
Pages
183 - 198
Database
ISI
SICI code
1386-1964(199912)431:2<183:HMIVIH>2.0.ZU;2-Z
Abstract
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.