Genetic Ancestry Matters in Childhood Leukemia Treatment Success

Published: 18 Mar 2022

Researchers from the NUS Yong Loo Lin School of Medicine and St Jude Children's Research Hospital in the USA have shown that it is important

Photo Credit: Burst

Researchers from the NUS Yong Loo Lin School of Medicine and St Jude Children’s Research Hospital in the USA have shown that it is important to consider race and genetic ancestry when treating acute lymphoblastic leukemia (ALL) in children.

The team studied the impact of genetic ancestry on childhood ALL, the most common type of childhood cancer. They found that ancestry itself is associated with differences in biology of ALL, and is also an independent factor contributing to differences in treatment outcomes.

The doctors evaluated an international cohort of more than 2,400 children, including more than 400 pediatric patients from Singapore and malaysia, to determine how genetic ancestry affects leukemia biology and outcomes under modern therapy. They found that several molecular subtypes were associated with East Asian ancestry (eg Chinese children). They also established that South Asian (eg Indian) and East Asian children have one of the best survival outcomes in the world. The findings were published in the March edition of JAMA Oncology.

While children with East Asian ancestry had survival rates similar to those of Caucasian children, previous research has shown that their genetic makeup showed genetic variations that render some medicines highly toxic for them, said Dr Shawn Lee, the lead author of the study and a Consultant in the Division of Pediatric-Hematology Oncology at the National University Hospital who is currently on a research fellowship at St Jude Children’s Research Hospital in Tennessee, USA.

Racial disparities exist in both the incidence and treatment outcomes for childhood with ALL. Globally, researchers have noted that Caucasian and Asian children do better than Blacks or Hispanics/Latinos. Locally and regionally, pediatric oncologists like Associate Professor Allen Yeoh, Senior Consultant in the Division of Pediatric Hematology-Oncology in NUH and co-investigator of the study, have observed for many years that Indian children seem to fare especially well, most of whom are cured. However, the exact reason for these racial differences are still not clear.

There is limited data on the genetic basis for such disparities. One main problem is that most of the studies and trials in childhood ALL currently are performed in Western countries (USA and Europe), with children of European descent (White/Caucasian children) forming the bulk of genomic studies, and only a small proportion of Asian children. There is therefore a lack of information on the genomics of Asian children in childhood leukemia.

“More importantly, this work, through showing the global racial diversity of childhood ALL, demonstrates the need to shift the overall paradigm of representation and diversity in cancer research. Currently, almost all therapies developed in ALL are based on Caucasian children, and the findings are then extrapolated to Asian children. For children in Singapore and other Asian countries, ALL (or cancer) therapy must take into account racial diversity. As we look to the next generation of therapies for ALL, it’ is essential that we consider the diversity of this cancer from an Asian perspective,” said Dr Lee.

Read more in the press release here.