Scientists Link Gene to Inherited Form of Childhood Leukemia

By Julie Grisham,

Tuesday, August 11, 2015

Child hand with IV holding adult hand.

A team led by MSK researchers has found that some cases of acute lymphoblastic leukemia in children may be linked to an inherited mutation in a gene called ETV6.

  • This is the second mutation found by the team from MSK and St. Jude’s.
  • ETV6 mutations were already known to play a role in some blood cancers.
  • The mutation was found in two families with a history of childhood leukemia.
  • Doctors may be able to screen for the mutation in families undergoing in vitro fertilization.

Researchers at Memorial Sloan Kettering and St. Jude’s Children’s Research Hospital (SJCRH) in Memphis have discovered a new genetic mutation associated with an inherited risk of childhood acute lymphoblastic leukemia (ALL). ALL is the most common childhood cancer, and children whose siblings have the disease carry a much higher risk of developing it themselves.

The mutation is in a gene called ETV6, which was already known to play a role in cancers of lymphocytes, the immune cells that circulate in the blood. Researchers observed the mutation in several children with leukemia in the same family cared for at Memorial Sloan Kettering and in another family treated at SJCRH.

Inherited Leukemia Syndromes

“This is now the second such syndrome of leukemia susceptibility we have described recently, suggesting that there is a significant proportion of childhood leukemia that is inherited,” says Kenneth Offit, Chief of the Clinical Genetics Service at MSK and the senior author of the new paper disclosing these findings, published jointly with researchers from SJCRH in the journal PLOS Genetics.

These findings suggest that many cases of childhood leukemia are inherited.

The joint MSK-SJCRH team previously identified another leukemia syndrome linked to a gene called PAX5. For the current study, Dr. Offit’s team at MSK carried out a series of experiments demonstrating that the ETV6 mutation observed in leukemia-prone families caused significant changes in the function of the gene.

The ETV6 mutation had been known to occur in leukemic cells, but until now researchers believed it happened later in the development of the cancer — called a somatic change — and was not inherited at birth. “What was particularly interesting about the families carrying the ETV6 mutations is that many did not have leukemia but had only low levels of platelets,” says Sabine Topka, a research fellow in Dr. Offit’s lab who was one of the lead authors. “This implies that other environmental or genetic factors also may play a role in those predisposed to leukemia.”

“This study is another fascinating example of the same gene alteration causing different symptoms in a patient — called pleiotrophism,” says MSK geneticist Vijai Joseph, another one of the lead authors. “In this case it leads to increased genetic risk for cancer.”

This discovery continues to provide insight into inherited causes of childhood leukemia.
Kenneth Offit
Kenneth Offit geneticist
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Understanding Hereditary Leukemia

“This discovery continues to provide insight into inherited causes of childhood leukemia,” Dr. Offit said. “It also allows us to prevent such leukemias in future generations by screening for these genes prenatally.” Prospective parents in families known to carry the gene mutation can seek in vitro fertilization that includes preimplantation genetic diagnosis, a technique that can identify embryos with genetic defects before pregnancy is attempted.

Ongoing studies will explore the frequency of inherited ETV6 mutations, as well as other genetic and nongenetic factors that modify its effect on leukemia risk.

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The study was made possible through support from the Robert and Kate Niehaus Clinical Cancer Genetics Initiative at Memorial Sloan Kettering, the Sandra Taub Research Award, the Sharon Levine Corzine Research Fund, the Lymphoma Foundation, the Filomen D’Agostino Foundation, the National Institutes of Health, and the American Lebanese Syrian Associated Charities of St. Jude Children’s Research Hospital. 


This is a very interesting discovery that there is indeed a gene linked to this form of leukemia.

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