A novel perspective on the pathogenesis of pediatric leukemia

In a recent study, scientists from the European Research Institute for the Biology of Ageing provide a novel perspective on the biological processes in childhood leukemia. On April 10, the research article “Clonal selection and asymmetric distribution of human leukemia in murine xenografts revealed by cellular barcoding” was published online in the journal Blood (http://www.bloodjournal.org/content/early/2017/04/10/blood-2016-12-758250).
Acute lymphoblastic leukemia (ALL) is the most common cancer in childhood, affecting ~100 children in the Netherlands each year. Although most children can be treated effectively, about 10-15% of patients develop a relapse that is difficult to treat and is the leading cause of cancer-related deaths in children. Previous studies have shown that leukemia in a single patient consists of multiple genetically diverse groups of cancer cells, so-called “clones”. The majority of ALL relapses is due to expansion of a clone that was already present at the time of diagnosis. Understanding how this clone escapes chemotherapy potentially allows developing new strategies to prevent leukemia relapse. However, due to a lack of methods to recognize individual leukemia cell clones, it is unknown how the number of leukemia clones changes over time and whether this contributes to the development of relapse in some patients..
A recent study by the Laboratory of Ageing Biology and Stem Cells describes a new method to identify and trace individual patient-derived leukemia cells. Using specifically designed genetic labels (“barcodes”), the authors were able to identify and trace the behavior of hundreds of human leukemia clones transplanted into mice. This is relevant, as existence of therapy-resistant leukemia clones in patients is thought to be the major cause of relapse. Remarkably, many of these clones were asymmetrically distributed over the skeleton, localizing to specific bones.
Currently, this approach is used mainly to understand the biological mechanism underlying leukemia. However, the approach may also increase our understanding of leukemia progression and contribute to novel strategies to understand and prevent leukemia relapse. For example, the transplantation and barcode assays could be used to investigate why some individual patient-derived leukemia clones are resistant to chemotherapy.