Research in zebrafish embryos may help explain the link between Max’s giant-associated protein (MGA) and Richter’s syndrome.
Previous studies showed that mutations in MGA are associated with a high risk of Richter’s syndrome, a rare lymphoma that can occur in patients with chronic lymphocytic leukemia.
Now, a team of biologists has discovered how MGA controls developmental processes. They described their discoveries in Developmental Cell.
“The same genes that are involved in building a person during embryonic development can mutate and cause cancer later in life,” said study author Scott Dougan, PhD, of the University of Georgia in Athens.
“No one has done a systematic study of MGA, but now that some studies connect it to cancer, there is tremendous interest.”
Preliminary tests have suggested that Richter’s syndrome might develop when MGA does not successfully control the activities of the MYC oncogene.
Dr Dougan and his colleagues decided to alter the levels of MGA in zebrafish embryos to see if they could discover any other roles for MGA.
They found that MGA also helps control the expression of bone morphogenetic proteins (BMPs). Specifically, a transcription factor complex consisting of MGA, Max, and Smad4 controls the expression of bmp2b/swirl in the zebrafish yolk syncytial layer. And this controls BMP signaling throughout the embryo.
BMPs are responsible for bone development in the embryo, but, in adults, changes in BMP activity can result in tumor development. This research suggests MGA may be part of this transformation.
“Scientists are only beginning to understand the roles this MGA protein plays, but our tests show that MGA may control many more processes than first imagined,” Dr Dougan said. “MGA may be involved in a number of other cancers, but we need to do more research before we’re sure.”
In the coming months, Dr Dougan and his colleagues plan to further examine the roles of MGA to determine when it controls MYC, when it controls BMP, and how it is involved in tumor formation.
“[W]e need investigations like these to understand the fundamentals of our biology,” Dr Dougan said. “Once we have this understanding, we can begin to develop new therapies to treat diseases in new, more effective ways.”
