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Infections early in life may activate immune responses that prevent leukemia

November 02, 2016
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New research from the Michael Cuccione Childhood Cancer Research Program at BC Children’s Hospital provides insight into how infections early in life may reduce the risk of leukemia, the most common type of childhood cancer.

“We have known about a link between early-life infection and reduced risk of children getting acute lymphoblastic leukemia for quite a long time,” says Dr. Gregor Reid, the lead author of the study. “This study provides the first description of immune mechanisms underlying this association.”

Dr. Reid is an Investigator with the Michael Cuccione Childhood Cancer Research Program at BC Children’s Hospital, an agency of the Provincial Health Services Authority, and Assistant Professor in the Department of Pediatrics at UBC. The study was published in the October 2016 issue of Leukemia.

Acute lymphoblastic leukemia (ALL) is the most prevalent type of childhood leukemia and is caused when abnormal white blood cells are transformed into leukemia cells. In a common form of ALL, the abnormal cells are called B-cell precursors (BCPs) and are often produced before birth. In these cases, children have a prolonged pre-leukemic phase, the period before leukemia develops.

Dr. Reid and his team found that when the immune system is exposed to infections during the pre-leukemic phase, the activated immune response may reduce the risk of leukemia developing. Simply, the receptors that recognize infections and initiate the immune response trigger the production of interferons. These interferons attack both the infection and the abnormal BCP cells, reducing their ability to turn into cancer. Researchers used a mouse model of leukemia for this study.

This new research could highlight potential targets for future treatment options and preventative measures that could slow down or stop the progression of leukemia.

“A better understanding of the immune responses that target the abnormal cells in ALL will enable us to develop more effective ways to harness these activities to stop leukemia returning in children who have undergone treatment,” says Dr. Reid.

Dr. Reid and his research team are now looking more closely at why early-life infections seem to be better at targeting abnormal BCP cells than those that occur in older children.

In BC, 30 per cent of childhood cancer patients are diagnosed with leukemia, with ALL being the most common form of the disease. ALL is treatable in over 90 per cent of cases in Canada; however, current treatments are unable to help all patients, and an average of 119 children die each year when their leukemia comes back after treatment.

Leukemia survivors experience life-long complications as a result of cancer and treatment, including neurocognitive impairments, organ dysfunction, and potentially the development of other cancers.  In all cases, children with leukemia and their families go through continuous physical, emotional and financial stress and often require additional support over the long term.

Funding:

This study was funded by grants to Dr. Gregor Reid from the Prevent Cancer Foundation, When Everyone Survives Foundation, the Michael Cuccione Foundation, the Canadian Institutes of Health Research, and a Career Development Award in Prevention from the Canadian Cancer Society. Funding also came from a BC Children’s Hospital Graduate Studentship to Mario Fidanza and a CIHR fellowship grant to Dr. Nina Rolf.

Key Collaborators:

  • Dr. Gregor Reid: Investigator, BC Children’s Hospital; Assistant Professor, Division of Hematology, Oncology and Bone Marrow Transplantation, Department of Pediatrics, UBC.
  • Mario Fidanza: Doctoral Student supervised by Dr. Gregor Reid.
  • Dr. Nina Rolf: Postdoctoral Fellow supervised by Dr. Gregor Reid.
  • Sumin Jo: Doctoral Student supervised by Dr. Peter van den Elzen and Dr. Gregor Reid.

Read More:

Fidanza M, Seif AE, DeMicco A, Rolf N, Jo S, Yin B, Li Y, Barrett DM, Duque-Afonso J, Cleary ML, Bassing CH, Grupp SA, Reid GS. Inhibition of precursor B-cell malignancy progression by toll-like receptor ligand-induced immune responses. Leukemia. 2016 Oct;30(10):2116-2119. PubMed PMID: 27220664.