12:19am Wednesday 23 October 2019

A genetic defect in sex cells may predispose to childhood leukemia


According to their findings published in Genome Research, the presence of a genetic defect in the egg or sperm from which children having ALL arise may be a prerequisite for the disease to develop. A significant number of children with ALL are thought to inherit a rare PRDM9 gene variant responsible for the abnormal sex cells–a gene variant that puts their own children at risk of having ALL-predisposed offspring.
“Our findings indicate ALL susceptibility to be partially hereditary. However, it is not classic heredity in the sense that the abnormal genetic variant does not need to be passed from parent to child for offspring to have the disease,” explains Julie Hussin, a doctoral student in Genomics under the direction of Dr. Philip Awadalla, a genetics researcher.

“Instead, the genetic defect in the egg or sperm from which the children developed is thought to predispose them to leukemia,” continues Julie Hussin. “However, only the children who inherit the genetic variant run the risk of transmitting ALL predispositions to their offspring.” According to the study, more than three fourth of families with affected children have an atypical form of the PRDM9 gene, but only half the patients inherited this genetic variant. The defect is expressed by chromosome recombinations at unusual points during gamete formation (eggs in girls, sperm in boys).

While an abnormal gamete may lead to ALL development, this condition alone is not enough. “Triggering the process of cancer cell proliferation inevitably requires a second hit, such as other mutations or environmental factors,” explains Julie Hussin.

Until now, few pediatric cancer studies have analyzed data from parents, as scientists generally focus on studying children, their tumors or their environment, especially during pregnancy. “Parents have to be included in these studies. Our findings demonstrate the importance of including parents’ genetic information for the understanding of childhood leukemia, as well as other early childhood diseases,” added Dr. Philip Awadalla, the lead principal investigator on the study.

The findings were replicated in a cohort of American children with ALL through a collaboration of the Sainte-Justine University Hospital Center in Montreal, Canada, and St. Jude Children’s Research Hospital in Memphis, USA.


Acute Lymphoblastic Leukemia Model of Heredity

At least one parent with/without leukemia produces abnormal gametes and carries a rare PRDM9 allele


Two Children

Both have leukemia, since each develops from an abnormal gamete

Child 1

Child 2

Receives the rare allele in its genome

Does not receive the rare allele

Produces abnormal gametes

Produces normal gametes

Risks having children with leukemia

Does not risk having children with leukemia


About the researchers:

Julie Hussin, doctorate student in bioinformatics

·         Sainte-Justine University Hospital Center, department of hematology/oncology

  • Department of biochemistry, Université de Montréal

Dr Philip Awadalla

·         Principal investigator, Sainte-Justine University Hospital Center

  • Professor, department of pediatrics, Université of Montréal
  • Principal investigator and scientific director, CARTaGENE

Scientific paper

·         « Rare allelic forms of PRDM9 associated with childhood leukemogenesis » in Genome Research, December 5, 2012.


Marise Daigle

Communication consultant
Sainte-Justine University Hospital Research Center
+ 1 514 345-4931, poste 3256


  • Julie Hussin and Dr. Philip Awadalla are available for interviews upon request.

Média contacts

Mélanie Dallaire (Québec)

Senior consultant, media relations,
Sainte-Justine University Hospital Center
514 345-7707
514 415-5727

William Raillant-Clark (Canada et ailleurs dans le monde)

International press attaché
Université de Montréal
1 514 343-7593

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