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John Dick
Dr. John Dick, Senior Scientist at Princess Margaret Cancer Centre, co-authored the study (Photo: Images by Delmar)

While treatment for acute lymphoblastic leukemia (ALL) continues to advance, about 40 per cent to 75 per cent of adult patients who receive treatment experience relapse. The prognosis for patients who relapse is poor. It is thought that while chemotherapies eliminate most leukemia cells, some resistant cells remain, and now researchers have narrowed in on why.

In a study recently published in Cancer Discovery, Dr. John Dick, Senior Scientist at Princess Margaret Cancer Centre, in collaboration with partners at St. Jude's Research Hospital, were able to isolate distinct populations of ALL cells called subclones and identify them as diagnosis relapse initiating (dRI) clones.

Using advanced genomic analysis on the cells, the team revealed that dRI clones differ from other leukemia cells and are somehow resistant to therapies. They are also present at diagnosis, meaning there is opportunity to improve targeted treatment at the onset for improved outcomes later.

The research is a companion piece alongside a study published in Blood Cancer Discovery in January. Together they describe the underlying properties of the clones that lead to ALL relapse.

"Our study has shown that genetic clones that contribute to disease recurrence already possess characteristics such as therapeutic tolerance that distinguish them from other clones at diagnosis," says Dr. Stephanie Dobson, first author of the study and member of Dr. Dick's Lab.

"Being able to isolate these clones at diagnosis, sometimes years prior to disease recurrence, has enabled us to begin to profile the properties allowing these particular cells to survive and act as reservoirs for relapse.

"This knowledge can be used to enhance our therapeutic approaches for targeting relapse and relapse-fated cells."

"Xenografting added considerable new insight into the evolutionary fates and patterns of subclones obtained from diagnosis samples," says Dr. Dick, who is also leader of the Ontario Institute for Cancer Research's (OICR) Acute Leukemia Translational Research Initiative and professor of molecular genetics at the University of Toronto.

"We were able to gather extensive information about the genetics of the subclones from our models, which helped us describe the trajectories of each subclone and the order in which they acquired mutations."

These findings open the door for future treatment options that could prevent the rate of relapse for patients with ALL.

The study was co-authored by Dr. Dick and Dr. Charles Mullighan of the St. Jude Department of Pathology.

This story has been adapted from the St. Jude Children's Research Hospital news release and OICR news.


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