Study Identifies New Set of Genes That May Explain Why People with Down Syndrome Have a Higher Risk of Leukemia

A study which appeared in the journal Oncotarget sheds light on why people with Down syndrome are at higher risk of Leukemia. Researchers pinpointed a new set of genes overexpressed in endothelial cells of individuals with Down syndrome, thus creating an environment conducive for leukemia.

Down syndrome occurs in approximately in one in 700 babies, and individuals with the syndrome not only development physical impairments, they have a greatly augmented risk of developing leukemia. Specifically, people with Down syndrome have a 500-fold risk of developing acute megakaryoblastic leukemia (AMKL) and a 20-fold risk of being diagnosed with acute lymphoblastic leukemia (ALL).

In this study, researchers used skin samples from patients with Down syndrome to create induced pluripotent stem cells (iPSC). They subsequently differentiated the iPSC cells into that were then endothelial cells. The researchers observed that the endothelial cell genetic expression produced altered endothelial function throughout cell maturation. “We found that Down syndrome, or Trisomy 21, has genome-wide implications that place these individuals at higher risk for leukemia,” says co-lead author Mariana Perepitchka, BA, Research Associate at the Manne Research Institute at Lurie Children’s via a press release. “We discovered an increased expression of leukemia-promoting genes and decreased expression of genes involved in reducing inflammation. These genes were not located on chromosome 21, which makes them potential therapeutic targets for leukemia even for people without Down syndrome.”

“Our discovery of leukemia-conducive gene expression in endothelial cells could open new avenues for cancer research,” said co-lead author Yekaterina Galat, BS, Research Associate at the Manne Research Institute at Lurie Children’s.

“Fortunately, advances in iPSC technology have provided us with an opportunity to study cell types, such as endothelial cells, that are not easily attainable from patients,” stated senior author Vasil Galat, PhD, Director of Human iPS and Stem Cell Core at Manne Research Institute at Lurie Children’s and Research Assistant Professor of Pathology at Northwestern University Feinberg School of Medicine. “If our results are confirmed, we may have new gene targets for developing novel leukemia treatments and prevention.”