SickKids scientists discover how mutations depress platelet production and increase leukemia risk

Researchers at The Hospital for Sick Children (SickKids) have shown for the first time how mutations in the ETV6 gene, that increase the risk of developing leukemia, can also interfere with production of platelets (blood cells responsible for clotting). The findings are published in the March 25 online edition of Nature Genetics.

In a collaborative effort, research teams led by Dr. Walter Kahr at SickKids and Drs. Jorge Di Paola and Christopher Porter at the University of Colorado used a wide-ranging genetic screen involving families in the United States and across Europe to identify two hereditary ETV6 mutations associated with increased leukemia susceptibility and low platelet counts.  They then set out to determine how these mutations affect cells.

It has been known for some time that when ETV6 is mutated in bone marrow cells there is an increased risk of childhood leukemia, which led researchers to describe ETV6 as a cancer-suppressor gene. Animal studies also linked ETV6 mutations to decreased platelet production. But it was not known how ETV6 mutations influenced cancer susceptibility and platelet development.

This study makes connections between inherited ETV6 mutations, cancer and platelet development in humans. The research demonstrated how mutant ETV6 exerts its effects in megakaryocytes (bone marrow cells that give rise to platelets) and most likely in other bone marrow cells involved in leukemia. These results have implications for the understanding of cell development and cancer. They also provide new targets for detecting hereditary susceptibilities in children for developing cancer and bleeding problems.