Chromatin conformation can guide the classification of leukemia, according to research published in Genome Biology.
Investigators mapped the conformation of the homeobox A (HOXA) gene cluster—11 genes encoding proteins that are highly relevant to many cancers—in a panel of leukemia cell lines.
And the team found they could use this information to distinguish subtypes of leukemia from one another.
“Previous studies have shown that looking at gene expression—the specific proteins produced by the genes—is a good predictor of whether patients have leukemia,” said study author Mathieu Blanchette, PhD, of McGill University in Montréal, Québec, Canada.
“We found that different types of leukemia cells also have a distinctive chromatin interaction—how the chromatin that makes up the genome is folded.”
The investigators used 5C chromosome conformation capture technology to analyze the HOXA gene cluster and then used the data to train and test a support vector machine classifier called 3D-SP.
They found 3D-SP could distinguish leukemias expressing MLL-fusion proteins from those expressing wild-type MLL. It could also classify leukemia subtypes according to MLL fusion partner.
The team noted that it is not clear whether the genome shape plays a role in causing leukemia or whether the leukemia causes the genome to change shape. And additional studies are needed to determine whether genome shape is as useful for classifying other types of cancer.
“Our study validates a new research avenue: the application of 3D genomics for developing medical diagnostics or treatments that could be explored for diseases where current technologies, including gene expression data, have failed to improve patient care,” said Josée Dostie, PhD, also of McGill University.
“While the use of 3D genomics in the clinic is still remote when considering the technical challenges required for translating the information to the bedside, we discovered a new approach for classifying human disease that must be explored further, if only for what it can reveal about how the human genome works.”
