Three new subgroups of juvenile myelomonocytic leukaemia, identified in two separate Nature Communications papers this week, can predict patient outcome, including patients most likely to experience spontaneous resolution of disease.
Juvenile myelomonocytic leukaemia (JMML) is an aggressive childhood cancer with limited treatment options. Current clinical and genetic markers of JMML do not explain the varied clinical outcomes associated with this disease. DNA methylation, a type of chemical modification that alters the way genetic information is used in different cells, has important roles in cancer. Two independent studies demonstrate that this so-called epigenetic marker could help to explain the variation in JMML patient outcome.
Christoph Plass, Daniel Lipka and colleagues analysed the DNA methylation patterns and mutation profiles of 167 JMML samples, identifying three distinct subgroups with varying levels of methylation (high, intermediate and low levels of methylation). They note that patients in the high methylation group have poor clinical outcome and the low methylation group have a good prognosis, and all three groups have different mutational profiles that suggest a link between activation of DNA methylation machinery and mutational patterns in JMML. Elliot Stieglitz, Mignon Loh and colleagues investigated the DNA methylation of 39 patients, and independently identified the three DNA methylation groups with high methylation linked to poor clinical outcome and low methylation linked to good prognosis, which they validated in a further 40 patients.
This research provides a basis for stratifying JMML patients based on DNA methylation, and helps develop our understanding of the underlying biology of this aggressive and complex disease.
DOI: 10.1038/s41467-017-02177-w | Original article
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