TP53 Gene Mutations Associated With Poor Prognosis In Myelodysplastic Syndromes (ASH 2011)
Published: Feb 22, 2012 12:43 pm
Researchers from King’s College Hospital in London have found that mutations in the TP53 gene are highly correlated with poor prognosis in myelodysplastic syndromes patients.
In a statistical analysis that controlled for a range of patient characteristics, the researchers found that having a TP53 mutation was the patient characteristic with the strongest impact on survival.
The findings were presented at the American Society of Hematology (ASH) annual meeting in December.
TP53 is a gene used by the body to produce a protein that suppresses tumor growth. The gene is mutated in about half of human cancers.
Previous studies have shown that TP53 mutations are associated with disease progression in MDS patients with severely low platelet counts (see related Beacon news) as well as MDS patients with a deletion in chromosome 5 (see related Beacon news).
In this study, the researchers screened 318 MDS patients for TP53 mutations. The median patient age was 65 years. Sixty-three percent of patients were categorized as low risk, 11 percent as intermediate risk, and 21 percent as high risk; 5 percent of patients could not be categorized due to missing data.
The researchers found TP53 mutations in 30 patients, or 9 percent of the sample.
The majority of the mutations (67 percent) were found in higher-risk patients, and many of these patients had three or more chromosomal abnormalities. The remainder of the mutations were found in lower-risk MDS patients with a deletion in chromosome 5.
The researchers found a total of 39 different mutations in TP53. Thirty percent of patients with a TP53 mutation had two types of TP53 mutations. The other 70 percent of patients had just a single mutation in TP53.
Of the patients with two TP53 mutations, 89 percent had less than 10 percent immature bone marrow cells. None of the patients with a deletion in chromosome 5 had two TP53 mutations.
The researchers then examined the bone marrow cells of the patients who had TP53 mutations. Not all bone marrow cells contained the mutations. They found a median of 42 percent of the bone marrow cells had TP53 mutations. In patients with two different TP53 mutations, 82 percent of bone marrow cells had TP53 mutations.
Nine patients with TP53 mutations were tested for the proportion of mutated bone marrow cells after treatment with Vidaza. The researchers found that 44 percent of patients had a reduced number of bone marrow cells with TP53 mutations, 44 percent maintained a stable proportion of bone marrow cells with TP53 mutations, and 11 percent experienced an increase in the number of mutated bone marrow cells.
After a median follow-up time of 18.7 months, the researchers found that patients without mutations in TP53 had better progression-free and overall survival times (median not yet reached for both), compared to patients with TP53 mutations (medians of 8.5 months and 9.7 months, respectively).
They observed the same trend for patients with three or more chromosomal abnormalities. Those without TP53 mutations had significantly better median progression-free survival and overall survival times (13.9 months and 14.1 months, respectively) than those with TP53 mutations (8.3 months and 9.6 months, respectively).
Similarly, patients with a deletion in chromosome 5 as their sole chromosomal abnormality who did not have mutations in TP53 had better median overall survival times than patients with TP53 mutations (66 months versus 23 months).
When the researchers controlled for patient age, gender, MDS type, risk of disease progression, transfusion dependency, and presence of chromosomal abnormalities, mutations in TP53 were the strongest independent predictor of progression-free survival and overall survival.
For more information, please see abstract 792 at the ASH 2011 meeting website.
- Mutations In Gene TP53 May Indicate Progressive Disease In Lower-Risk MDS Patients With Chromosome 5 Deletion
- Mutations In Chromosome 7 Are Associated With Better MDS Prognosis Than Other Chromosomal Abnormalities (ASH 2010)
- IDH1 Mutations Found To Have ‘Powerful’ Impact On Survival In Myelodysplastic Syndromes Patients
- Half Of MDS Patients With Chromosome 5 Deletion Also Have Important Genetic Mutations
- Trisomy 8 May Not Affect The Prognosis Of Certain MDS Patients