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International collaboration yields insights into childhood leukemia risk

By joining forces, researchers at St. Jude Children’s Research Hospital and the Institute for Cancer Research UK have discovered new genetic variants associated with B-cell acute lymphoblastic leukemia risk.

Memphis, Tennessee, November 25, 2019

Dr. Jun Yang contemplates the results of his study

Dr. Jun Yang was part of a team of researchers that discovered a gene variant common in a pediatric and adult leukemia. 

A study led by St. Jude Children’s Research Hospital and the Institute for Cancer Research UK revealed previously unknown genetic associations for B-cell acute lymphoblastic leukemia (ALL) risk. The collaboration generated one of the largest cohorts ever assembled for such an analysis. The findings appear today in Nature Communications.

The researchers focused on the most common subtypes of ALL: those harboring ETV6-RUNX1 genetic fusions and those with extra chromosomes, called hyperdiploid. ETV6-RUNX1 fusion-positive and hyperdiploid each make up 20-25% of pediatric ALL. Both subtypes are specific to children and occur rarely in adult populations.

“We want to make discoveries that lead to new understanding of ALL and its genetic risk,” said co-corresponding author Jun J. Yang, Ph.D., of the St. Jude Departments of Pharmaceutical Sciences and Oncology. “But we also want to invite others to start looking at these genes to figure out why they are important to leukemia, and ultimately to aid in the development of new therapies.”

Fetal development protein linked to ALL

By pooling data from collaborative groups in the U.S. and U.K., the researchers analyzed more than 5,000 leukemia cases and 16,000 control cases making a cohort of more than 21,000 samples.

In the ETV6-RUNX1 subtype, the researchers found a variant in the gene IGF2BP1. The research suggests that the ETV6-RUNX1 fusion revs up expression of IGF2BP1. IGF2BP1 is a fetal development protein that normally turns off after birth. The ETV6-RUNX1 fusion is likely to turn this growth protein back on, contributing to the development of ALL.

An unappreciated link to adult leukemia

Chronic lymphocytic leukemia (CLL) occurs in adults, often in the elderly. Researchers know that different biology underlies CLL and ALL. However, there may be a link between the two diseases.

In hyperdiploid ALL, the researchers found a variant in the gene BAK1. This variant is also found in CLL. In addition, the variant is associated with the production of several types of blood cells. This common biology between these two types of leukemia has never before been documented.

“Together, we created a cohort that let us dive deeply into the biology underlying genetic findings that are important for this pediatric cancer, ” said co-corresponding author Richard Houlston, M.D., Ph.D., of the Institute for Cancer Research. “These findings also led us to question the different biology between childhood and adult leukemia.”

The team identified two other variants with B-cell ALL risk, but the function of these variants remains a topic for further research.

The study’s first authors are Jayaram Vijayakrishnan of the Institute for Cancer Research and Maoxiang Qian of Fudan University and formerly of St. Jude. The study’s other authors are Wenjian Yang, Ching-Hon Pui, William Evans, Wentao Yang, Chunliang Li, Charles Mullighan and Mary Relling of St. Jude, as well as researchers from 13 other institutions.

The research at St. Jude was funded in party by grants (CA21765, CA98543, CA114766, CA98413, CA180886, CA180899, GM92666, GM115279 and GM097119) from the National Institutes of Health and ALSAC, the fundraising and awareness organization of St. Jude.

St. Jude Children's Research Hospital

St. Jude Children's Research Hospital is leading the way the world understands, treats and cures childhood cancer and other life-threatening diseases. It is the only National Cancer Institute-designated Comprehensive Cancer Center devoted solely to children. Treatments developed at St. Jude have helped push the overall childhood cancer survival rate from 20% to 80% since the hospital opened more than 50 years ago. St. Jude freely shares the breakthroughs it makes, and every child saved at St. Jude means doctors and scientists worldwide can use that knowledge to save thousands more children. Families never receive a bill from St. Jude for treatment, travel, housing and food — because all a family should worry about is helping their child live. To learn more, visit or follow St. Jude on social media at @stjuderesearch.