Using multivariable models and weighted correlation network analysis (WGCNA), the researchers found co-occurrences of gene expression clusters and mutational events with respect to ibrutinib response. The researchers also found a potential role for FLT3 pathway inhibitors in select patients. A median of 13 somatic variants (range, 1–80) was found per patient.

Karen Ballen, MD, professor of medicine at the University of Virginia in Charlottesville, noted that the whole exome gene sequencing that was performed revealed a multitude of genetic mutations. In addition, response to antileukemia drugs was shown to correlate with mutational status in some cases.

“This is a formidable endeavor and illustrates the power of multicenter collaboration,” Dr Ballen told Hematology Advisor. “There are FDA-approved drugs for only 3 of these mutations, and these have been studied previously, so the paper has no immediate clinical impact. It does, however, show the path forward for using genetic mutations to select drugs or combinations of drugs for patients with AML.”

Currently, AML has a low survival rate, with fewer than 25% of newly diagnosed patients surviving beyond 5 years. Developing effective, targeted AML therapies is challenging because AML is a disease of many types.

“The field is moving quickly. We are grateful to the patients who donated blood or bone marrow for these studies with the recognition that this will help the next generation of patients with AML, and we are hopeful that through these studies, and through ongoing and future clinical trials, we will see substantial improvement in outcomes for patients diagnosed with AML,” said Dr Druker.


1. Tyner JW, Tognon CE, Bottomly D, et al. Functional genomic landscape of acute myeloid leukaemia [published online October 17, 2018]. Nature. doi: 10.1038/s41586-018-0623-z