Leukemia research yields promise of treatment
Bill Sanford will be honoured for work on promising leukemia treatment
Every morning when Bill Stanford looks in the mirror he is reminded of why he does what he does.
The world-renowned genetics and stem cell researcher who works at The Ottawa Hospital and the University of Ottawa, has a tattoo on his forearm that, in flowing mirror-image script, spells f—k you cancer.
He got the tattoo a year ago while taking a break from a conference in Washington, D.C. Two of his friends had just died of cancer, within 21 hours of each other, and Stanford was angry. “I was really pissed off that my friends died of cancer and was pissed off even more because I work on cancer and I was taking it personally.”
In addition to the words written backwards (“I can’t insult everyone that I run across”), the tattoo includes a colourful series of dots connected with lines that represent some of the potentially life-saving research Stanford is working on. For him, it was a way of finding something positive in the pain.
That research, which Stanford now wears on his arm, led him and his team to a possible treatment for deadly chemotherapy-resistant acute myeloid leukemia and a diagnostic test to determine which patients would benefit.
The research has, so far, been done in mouse models. Stanford is anxious for a clinical trial to get underway using already developed drugs that block MDM2, a gene that helps acute myeloid leukemia cells resist chemotherapy, with deadly consequences for patients.
In the mouse model, the experimental treatment put 100 per cent of the animals into complete remission, while those that received the current standard treatment all died. Caryn Ito, a senior investigator at The Ottawa Hospital, who is married to Stanford, developed the mouse models and co-led the study.
“We were blown away when we saw the results,” said Stanford. “If these findings hold up in clinical trials, we could have a new treatment for people who would almost certainly die of their disease today.”
Stanford’s research, published in the leading cancer journal Cancer Discovery, focused on a protein called MTF2, which plays a role in blood development. The protein places chemical tags near certain genes to help control their expression. Using samples from patients treated at The Ottawa Hospital, the team found that patients with normal MTF2 activity were three times more likely to be alive after five years than those with low MTF2 activity.
They took that information and discovered that MTF2 plays a role in a gene that helps cells resist chemotherapy. But when MTF2 activity is low, it is unable to do so and that gene, MDM2, resists chemotherapy drugs.
Since drugs are already being developed that block MDM2, Stanford’s research team tried it on mice with advanced acute myeloid leukemia with encouraging results. The drug must now be tested in a clinical trial, but Stanford is optimistic the research represents a significant milestone in the treatment of acute myeloid leukemia.
The discovery is among research for which Stanford will be honoured when he receives The Ottawa Hospital’s Chrétien Researcher of the Year award on Oct. 27.
It is also a high point in a career that has been shaped by contact and inspiration from those who might benefit from his work.
Stanford, who grew up in the U.S., was born into a family that emphasized working for public good. His father was a lawyer who, in his spare time, worked with groups to promote legislation that would benefit the disabled. His mother, an educator, did volunteer work. And together, the family ran a summer program for disabled students that benefitted people like Stanford’s brother who was disabled as a result of a genetic disorder called Charge Syndrome.
Stanford was always interested in science, but says he didn’t want to be a doctor after witnessing all the surgeries and treatments his brother had to endure.
But over his career, he has gradually been pulled, by patients, from basic research toward developing new treatments.
Catherine Lawrence, a Toronto lawyer-turned-standup comic who suffers from an incurable lung disease, contacted Stanford with the help of a “laughter basket” and convinced him to work on treatment or a cure for her disease.
In his Ottawa office, Stanford opens drawers and pulls out giant clown glasses, a tiny rubber chicken and an orange feathery boa — all from Lawrence — that were part of her campaign to bring his expertise to focus on finding treatment for her disease, LAM, which stands for lymphangioleiomyomatosis The rare, progressive lung disease usually strikes women in their prime.
Stanford’s lab now spends about one-third of its time working on leukemia, one-third on LAM and one-third on other projects, including aging. Others working on treatment for the lung disease believe a cure is possible within their lifetimes.
“I truly believe we are making a difference.”
Meeting some of the patients who contributed cells to his leukemia research, meeting Lawrence and other LAM patients, he said, has been motivating.
“It has felt good to make some progress.”
And Stanford said the tattoo helps to remind him of that.
“When I look in the mirror in the morning, it reminds me of what the hell I am doing up and going to work for.
“I think being angry at a disease is perfectly acceptable.”
When I look in the mirror in the morning, it reminds me of what the hell I am doing up and going to work for.