What the study of the mutant gene behind aggressive adult leukaemia can offer for treatment

Discover how TP53 mutations in adult leukaemia impact treatment outcomes and potential strategies for improved patient care.

Certain kinds of mutations in gene TP53, which encodes the p53 tumour suppressor protein, often dubbed the ‘guardian of the genome’, could perhaps be making acute lymphoblastic leukaemia (ALL) one of the hardest cancers to treat, new research has found.

The study, led by Caner Saygin, assistant professor at the University of Chicago Medicine, was recently published in the Blood Cancer Journal, a press release said.

Acute lymphoblastic leukaemia or acute lymphocytic leukaemia is a type of blood cancer that affects the white blood cells and bone marrow. It is a fast-growing cancer. It is the most common type of paediatric cancer. When it affects adults, it is considered challenging to treat.

A paper published in Cureus in 2024, by Dinesh N. Nalage et al on leukaemia in India, states that leukemia ranked 6th in incidence among all cancers (excluding other neoplasms) from 1990 to 2019, accounting for 4.83% of total cancers. Males are more likely to have leukemia than females, with a 2.24% higher incidence in males. In terms of subtypes, ALL was the number one cause of DALYs and deaths in India in 2019 for both boys and girls aged 0 to 20. While the proportion of ALL declined in both sexes between 1990 and 2019, ALL caused 15.24% of fatalities in men in 2019, while the proportion of mortality in females due to ALL was 10.59% that year.

The p53 tumour suppressor protein is stopping for cell division when DNA is damaged, and for initiating repairs. If the damage is irreparable, it is meant to trigger apoptosis, or programmed cell death. But what happens if this does not work as it should? In a healthy cell, TP53 acts as both a brake and an emergency stop button. When DNA gets damaged, this gene either halts the cell to make repairs or orders it to self-destruct before it causes harm. But when the gene mutates, these safety systems fail. The broken cell can keep dividing even while out carrying genetic mistakes, which then pile up until cancer forms.

“In earlier lab work, we found that TP53-mutant ALL cells have increased growth signals and defective cell-death pathways,” Dr. Saygin said, as per the release. “When treated with chemotherapy, these cells accumulate DNA damage, but they don’t die the way they should because the apoptosis pathways are broken, so they persist and eventually cause relapse. That’s why these cancers are so hard to eliminate with standard therapy alone.”