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'We cannot accept that acute myeloid leukemia kills one patient out of three'

cellot_sonia_webDespite rapid advances in treatment for some forms of pediatric leukemia, only around 60 per cent of children diagnosed with acute myeloid leukemia (AML) survive - a grim statistic that is motivating TFRI researcher Dr. Sonia Cellot’s work.

AML is the most deadly form of the disease, with cure rates significantly lower than some other forms of leukemia. Cellot's goal is to identify epigenetic regulators of leukemic stem cells to eventually help contribute to therapeutic drug design.

“This is clearly not an area we are doing well in,” says Dr. Cellot, trained initially in pediatric hematology and currently based at CHU Sainte-Justine in Montreal. “We don’t have the cure rates as high as in other areas of leukemia, so this is a big focus for me.”

An emerging and fascinating concept is that some epigenetic regulators are critical to sustain leukemic cells, says Dr. Cellot, but appear to be dispensable for normal hematopoietic stem cells (HSC) function.

“The idea would be to find something we could target to eradicate the leukemic stem cell while preserving the normal blood stem cell compartment,” she says. Stem cells are located in bone marrow and stay with people throughout their lives, says Dr. Cellot.

The cells consequently have time to accumulate a number of mutations, making them frequent targets of malignant transformation that can lead to fullblown leukemia.

“Especially in young children, the genetic defect which occurs is very potent and has a very high ability to transform the cells,” says Dr. Cellot. “It’s an aggressive cancer, but the important thing is to find a way to tackle it.”

Bone marrow transplantation procedures used to cure certain types of cancer also rely on stem cells to resume blood production in patients, adds Dr. Cellot, noting that a better understanding of their biology could lead to increased transplantation success.

Dr. Keith Humphries, BC Cancer Agency, is mentoring Dr. Cellot for the duration of her three-year award.

“Sonia’s insightful perspective gathered from infant leukemia patients inspired her studies on the role of epigenetic regulators in HSC fate determination,” he says. “She is in an ideal position to build bridges between her fundamental research program and improved therapies.”

Dr. Cellot believes TFRI’s New Investigator awards are a “lifesaver” for young cancer researchers across the country. “It’s amazing that TFRI helps us young ones establish our labs,” she says. “It’s crucial if we want to continue this type of research in Canada.”

Patient Story: 

Léa Legault: http://www.tfri.ca/en/OurWork/patient-stories/blood-cancers/lea-legault

Project Title: Deciphering the role of chromatin demethylases in high risk pediatric acute myeloid leukemia
Award: $450,000 over three years
Mentoring Program: The Terry Fox New Frontiers Program Project Grant in Core Pathogenic Pathways in Human Leukemia
Mentors/PIs: Dr. Keith Humphries

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