Abstract
We examined chromosomes and molecular aberrations in 21 patients with therapy-related leukemias (t-AML) or myelodysplastic syndromes (t-MDS). All patients showed abnormal karyotypes, and chromosomal losses of No. 5 and/or No. 7 (−5/5q− and/or −7/7q−) were identified in 12 patients. Among these 12, six patients (50%) harbored a TP53 mutation, and two of five examined showed microsatellite instability, suggesting replication error (RER+) phenotype. Meanwhile, among the other nine patients without −5/5q− and/or −7/7q−, none harbored a TP53 mutation, and none of five examined showed RER+ phenotype. Thus, TP53 mutations and RER+phenotype were preferentially associated with specific chromosomal losses in t-AML/MDS. We then screened for mutational events in representative DNA mismatch repair genes; exons 5–7 and 12–15 of the hMSH2 gene and exon 9 of hMLH1. Notably, two unrelated patients showing RER+ phenotype had an identical missense alteration at codon 419 of hMSH2 in their marrow cells and fibroblasts, which were not found in 120 DNA samples from healthy volunteers or patients with other hematological disorders. Consequently, this study revealed a possible relationship of RER+ phenotype accompanying an hMSH2 alteration to the development of therapy-related AML/MDS in association with TP53 mutations and specific chromosomal losses, and suggests that some patients may be predisposed to myelodysplasia after chemotherapy for their primary tumor.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Horiike, S., Misawa, S., Kaneko, H. et al. Distinct genetic involvement of the TP53 gene in therapy-related leukemia and myelodysplasia with chromosomal losses of Nos 5 and/or 7 and its possible relationship to replication error phenotype. Leukemia 13, 1235–1242 (1999). https://doi.org/10.1038/sj.leu.2401466
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.leu.2401466
Keywords
This article is cited by
-
TP53 mutation in newly diagnosed acute myeloid leukemia and myelodysplastic syndrome
Diagnostic Pathology (2021)
-
Risk factors for de novo and therapy-related myelodysplastic syndromes (MDS)
Cancer Causes & Control (2021)
-
Genetic Pathway in the Pathogenesis of Therapy-Related Myeloid Neoplasms: A Literature Review
Oncology and Therapy (2020)
-
Complex molecular genetic abnormalities involving three or more genetic mutations are important prognostic factors for acute myeloid leukemia
Leukemia (2016)
-
The prognostic impact of 17p (p53) deletion in 2272 adults with acute myeloid leukemia
Leukemia (2009)