Acute myeloid leukemia (AML) is an aggressive blood cancer that arises when normal blood cell development goes awry.
However, the disease does not follow a single pathway — each patient's leukemia grows and develops in its own unique way.
Understanding these differences has long been a challenge, but new research from UHN's Princess Margaret Cancer Centre (PM) offers a clearer picture.
A team led by Dr. John Dick, a Senior Scientist at PM, analyzed more 1.2 million leukemia cells from 318 AML patients, comparing them to a detailed atlas of healthy blood cells.
This large-scale mapping effort revealed 12 key patterns of leukemia cell growth and development, showing how different genetic mutations drive the disease in distinct ways. Some leukemia cells resembled early-stage blood stem cells, while others mimicked more developed blood cells — findings that challenge traditional classifications of AML.
"These discoveries redefine how we see AML," says Dr. Dick, the study's senior author who is also a Helga and Antonio De Gasperis Chair in Blood Cancer Stem Cell Research at PM and a professor of molecular genetics at the University of Toronto (U of T).
"By understanding how leukemia cells develop, we can create treatments that precisely target a patient's unique cancer."
Andy Zeng, an MD/PhD student in Dr. Dick's lab at the U of T, is the first author of the study.
This research has immediate implications.
Doctors could use these leukemia growth patterns to classify AML more accurately, leading to better treatment decisions.
It also paves the way for personalized therapies that attack cancer at its root, based on its specific developmental pathway.
Looking ahead, this map of leukemia's hidden patterns could help researchers develop drugs that push leukemia cells back toward normal development—an approach known as differentiation therapy.
This work was supported by The Princess Margaret Cancer Foundation, the Canadian Cancer Society, the Ontario Institute for Cancer Research, the Canadian Institutes for Health Research, the University of Toronto's Medicine by Design initiative with funding from the Canada First Research Excellence Fund, the Ontario Ministry of Health, a Canada Research Chair, and the Terry Fox Foundation.
Dr. John Dick has received research funding from BMS/Celgene and holds intellectual property licenses with Pfizer/Trillium Therapeutics. For a full disclosure of conflicts of interest, please review the publication.
