Myelodysplastic syndromes arising in patients with germline TP53 mutation and Li-Fraumeni syndrome

Sameer S. Talwalkar, C. Cameron Yin, Rizwan C. Naeem, M. John Hicks, Louise C. Strong, Lynne V. Abruzzo

Research output: Contribution to journalArticlepeer-review

48 Scopus citations


Context.-Li-Fraumeni syndrome (LFS), characterized by predisposition to early onset of a variety of malignancies, is usually associated with germline mutation of the tumorsuppressor gene, TP53. Mutation carriers are at increased risk of multiple primary tumors, many of which arise in previous radiation-therapy sites. In patients with LFS, acute myeloid leukemia is uncommon and myelodysplastic syndrome (MDS) is rare. Objective.-To evaluate the morphologic, cytogenetic, and molecular diagnostic findings of 3 unique cases of MDS arising in patients with germline TP53 mutation, 2 with classic LFS. Design.-We searched the Li-Fraumeni Syndrome Registry in the Department of Genetics at the University of Texas M. D. Anderson Cancer Center (Houston, Texas) and identified 3 patients with documented germline TP53 mutations or LFS who had developed MDS during a period of 6 years (2000-2005). The clinical, cytogenetic, and molecular diagnostic data and bone marrow aspirate smears and biopsies on all patients were reviewed. Immunohistochemical staining with antibody to p53 was also performed. Results.-Two patients met the criteria for classic LFS; one had no history of malignancy in first-degree relatives. The MDS followed chemotherapy and radiation therapy and progressed to acute myeloid leukemia in 2 patients. Cytogenetic analysis demonstrated chromosome 5 abnormalities in a complex karyotype in all cases. Two patients died, one of acute myeloid leukemia and one with glioblastoma multiforme, MDS, and persistent pancytopenia. Conclusions.-Patients with LFS may develop MDS, which is most likely therapy-related and is associated with cytogenetic markers of poor prognosis.

Original languageEnglish (US)
Pages (from-to)1010-1015
Number of pages6
JournalArchives of Pathology and Laboratory Medicine
Issue number7
StatePublished - Jul 2010
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Medical Laboratory Technology


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