TFRI-funded researchers at BC Cancer in a new study demonstrate that a genomic test known as whole transcriptome sequencing (RNA-seq) is the best available tool to accurately provide risk stratification and therapy selection for patients with acute myeloid leukemia (AML).
The study, published in Nature Communications (April 2021), provides evidence that this tool, if adopted clinically, could be used to help personalize treatments for patients with this disease.
“The work demonstrates that RNA-seq can be used as a clinically validated genomic test,” says Dr. Aly Karsan, a Distinguished Scientist at Canada's Michael Smith Genome Sciences Centre at BC Cancer, the study’s senior author. “Use of this assay clinically would provide a way to more accurately provide risk stratification for an individual patient, and also potentially provide opportunities to develop novel clinical trials.”
To reach this conclusion, the team compared the effectiveness of this tool against whole genome and exome sequencing using a large cohort of AML patients. After running a number of tests, they were able to determine that a standalone RNA-seq assay “offers the greatest diagnostic return, enabling identification of expressed gene fusions, single nucleotide and short insertion/deletion variants, and gene expression information,” according to Dr. Karsan.
Using this information, the team also created a gene expression signature called the AML Prognostic Score (APS) that searches for the expression of 16 genes to determine who is at a higher risk of developing serious disease.
“Impressively, the assay was able to move around 60% of patients out of an intermediate-risk category and into high- or low-risk sub-groups, thereby allowing better risk stratification for clinical management,” says Dr. Karsan.
The APS was also tested on pediatric patients with AML, and was found to work very well on these patients also. This implies that the final common pathways to poor-risk AML may be very similar in adults and pediatric patients.
That’s not all. The study also found that a subset of high-risk patients with dysregulated integrin signaling could potentially benefit from therapies that inhibit the focal adhesion kinase (FAK), setting the stage for the development of personalized treatments for these high-risk AML patients.
A clinical transcriptome approach to patient stratification and therapy selection in acute myeloid leukemia
T. Roderick Docking, Jeremy D. K. Parker, Martin Jädersten, Gerben Duns, Linda Chang,
Jihong Jiang, Jessica A. Pilsworth, Lucas A. Swanson, Simon K. Chan, Readman Chiu, Ka Ming Nip, Samantha Mar, Angela Mo, Xuan Wang, Sergio Martinez-Høyer, Ryan J. Stubbins, Karen L. Mungall, Andrew J. Mungall, Richard A. Moore, Steven J. M. Jones, İnanç Birol, Marco A. Marra, Donna Hogge & Aly Karsan
This study was partially funded by a Terry Fox New Frontiers Program Project Grant in Exploiting Pathogenic Mechanisms in Acute Leukemia for Clinical Translation