Treatment

Gene Mutation Linked To Therapy-Related Leukemia

By John Lugo

Histopathological image of acute myeloid leukemia. Courtesy of Washington University

A small percentage of cancer patients are diagnosed with leukemia after chemotherapy or radiation. This type of acute myeloid leukemia (AML) is almost always fatal.

Scientists hypothesized that the cancer treatment induced a reaction that was the reason for AML’s development. However, a recent study by researchers at the Washington University School of Medicine shows that the presence of p53 gene mutations in blood stem cells can appear well before a cancer diagnosis and that these mutated cells are more resistant to treatments, multiplying at a fast pace after exposure to chemotherapy or radiation treatment and leading to the development of AML.

P53 is a tumor suppressor gene, which can allow tumors to form if disabled by a mutation. With the information from the study, researchers and doctors hope to determine which patients are at risk for therapy-induced AML and look for different treatment approaches.

“Until now, we’ve really understood very little about therapy-related AML and why it is so difficult to treat,” said the study’s corresponding author Daniel Link, MD, a hematologist and oncologist at Siteman Cancer Center at Washington University and Barnes-Jewish Hospital, in a press release. “This gives us some important clues for further studies aimed at treatment and prevention.”

At the beginning of the study, the researchers sequenced genomes from 22 patients with therapy-related AML and saw they had comparable numbers and types of mutations as those who were diagnosed with AML without undergoing therapy. This showed that cancer therapy didn’t affect the overall number of mutations.

The researchers also studied the blood samples of 19 subjects between the ages of 68 to 89 who have never had cancer or chemotherapy and found that nearly half had mutations in one copy of p53, which signaled that the mutation may develop with age.

“We’re already conducting follow-up studies to look for other age-related mutations that may be at play in therapy-related AML,” Link said in the release. “As individuals, we’re not genetically homogeneous throughout our lives. Our DNA is constantly changing as we age, and we know this plays an important role in the development of cancer. With advanced genomics, we can investigate the interplay between aging and the random accumulation of mutations, as a means to improve the diagnosis, treatment and prevention of cancer.”

About 2,000 of the 18,000 cases of AML diagnosed each year in the United States are a result of previous therapies.