Juvenile myelomonocytic leukemia or JMML is a rare and aggressive childhood cancer. Only one in two children eventually survives the disease and new therapies are urgently needed. In a recently finished PhD project at Ghent University, researchers investigated which genes are inappropriately turned on or off in children with JMML. This opens up the possibility of developing new, targeted treatments.
The context
One in three men and one in four women in Belgium are diagnosed with cancer before the age of 75. Cancer arises if a body cell goes mad and starts dividing in places and at times at which this is not desirable. The resulting tumor can be found anywhere in the human body, from the breast to the prostate. However, a tumor can also be ‘liquid’ and occur in the bloodstream; in this case the cancer is called leukemia. Cancer in children occurs much less frequent than during adulthood, but is of course not less devastating. In this study, a rare and aggressive childhood leukemia was investigated, called juvenile myelomonocytic leukemia or JMML.
Yearly, one or two children are diagnosed with JMML in Belgium. However, there is currently no chemotherapy available. The children can only be saved by a stem cell transplantation, a tough procedure with several side effects, for which also an appropriate donor has to be found. Survival rates are worse compared to other – and more frequent – types of childhood leukemia since only one in two patients eventually survives the disease. The need for an alternative treatment is thus very high.
The nuts and bolts
In this research project, the RNA of 82 children with JMML was investigated, more than any other study so far. RNA is the more active nephew of DNA and gives us an idea of which genes are active or inactive at a specific moment in time. Using RNA, the status of more than 50.000 genes was evaluated. The results of children with JMML were compared with healthy children.
Based on this comparison, a piece of RNA was described that plays an important role in JMML. The piece of RNA originates from a gene called LIN28B and was already known in other types of childhood and adult cancer. Interestingly, the gene is normally only active before birth to cope with the enormous growth requirements of a developing embryo. After birth, LIN28B is turned off. However, it can be reactivated in different types of cancer, leading to undesired cell growth. The specificity of LIN28B expression is an important feature for the development of new therapies. Indeed, the Holy Grail in cancer treatment is the development of drugs that only target the diseased cells but not the healthy cells. Since LIN28B is only active in cancer cells, the possibilities for developing targeted therapies increases.
How will this help me?
Often several years expire between the discovery that a certain gene is important in a specific disease and the availability of new drugs. The gene first has to be investigated in more detail. Follow-up experiments in cell cultures and mice revealed a complete network of other genes influenced by LIN28B. These results are a significant step in understanding the disease, and can be built on by other researchers to work towards a targeted therapy for children with JMML.