TP53 allelic state is critical for diagnostic and prognostic precision in blood cancer

12 August 2020

A double mutation in TP53 gene deteriorates the prognosis of a rare form of blood cancer. If there is only one mutation or no mutation, then the prognosis is better. This appears from an international study, led by the Memorial Sloan Kentering Cancer Center in New York, in which Amsterdam UMC and Radboudumc participated. The study was published in Nature Medicine

The research was done on TP53, a gene that often mutates in several types of cancer. The researchers examined whether the gene mutates zero, once or twice in a rare form of blood cancer, myelodysplastic syndrome (MDS), a precursor of acute myeloid leukemia. A study of more than 4,400 patients revealed the worse prognosis for a double mutation. 

The TP53 gene and treatment options

Joop Jansen, theme Cancer development and immune defence, explains: "This research shows that the double TP53 mutation is even the most important variable for predicting the course of the disease. Therefore, the impact of zero, one or two mutations in the TP53 gene should also be investigated for other types of cancer. For TP53 mutations are common in other types of cancer." In many types of cancer, mutations in TP53 are associated with much worse results, such as recurrence of the disease and shorter survival.

Co-researcher Arjan van de Loosdrecht, professor of Hematology at Amsterdam UMC, adds: "These findings are immediately clinically relevant for risk assessment and treatment for people with this type of blood cancer. People who do not have a double mutation do not necessarily have a very poor prognosis as we previously assumed. If there is a double mutation in TP53, physicians should consider proposing an intensive treatment plan, given the poorer prognosis, including a donor stem cell transplant".

For the entire study see Nature Medicine and the press release of Memorial Sloan Kentering.