A Hidden Cellular Structure Could Revolutionize How We Treat Leukemia
Deep within the cell, a previously unseen structure is challenging everything scientists thought they knew about leukemia. What once appeared as chaotic under the microscope actually follows a remarkably simple physical principle—a principle that ties together multiple major genetic mutations behind this disease.
Researchers at Baylor College of Medicine have uncovered that various genetic drivers of leukemia exploit the same secret compartments within the cell nucleus to sustain cancer growth. This discovery points to a common physical target, opening the door to innovative treatments that could attack a shared vulnerability across different genetic forms of leukemia.
Traditionally, leukemia begins when mutations in blood-forming stem cells disturb the delicate balance between growth and differentiation. Strikingly, patients with entirely different genetic changes often exhibit remarkably similar patterns of gene activity and can respond to the same therapies. But what invisible mechanism causes such diverse mutations to behave so similarly?
To investigate this mystery, the Riback and Goodell laboratories at Baylor joined forces. Dr. Joshua Riback, an assistant professor and CPRIT Scholar specializing in how proteins form droplets through a process called phase separation, teamed up with Dr. Margaret “Peggy” Goodell, chair of the Department of Molecular and Cellular Biology and a pioneer in studying blood stem cells and leukemia. Together, they sought to uncover the hidden physics underlying cancer’s complex chemistry.
The breakthrough came in a moment of unexpected clarity. Graduate student Gandhar Datar, co-mentored by Riback and Goodell, peered through Riback’s high-resolution microscope and observed something astonishing: the nuclei of leukemia cells were dotted with a dozen bright, shimmering spots—tiny beacons completely absent in healthy cells.
These spots were far from random. Packed with large amounts of mutant leukemia proteins, they also attracted normal cell proteins, orchestrating the activation of leukemia-related genes. The researchers realized these were entirely new nuclear compartments formed via phase separation, a physical principle similar to how oil droplets appear in water. They named these compartments “coordinating bodies,” or C-bodies.
Within the nucleus, C-bodies act like miniature control hubs, gathering molecules that keep leukemia genes active. Just as drops of oil float to the surface of soup when the ingredients reach the right balance, these structures form when the molecular conditions in the cell align perfectly.
Even more surprising, leukemia cells with completely different mutations produced droplets behaving in the same way. While the biochemical details varied, the resulting nuclear condensates carried out identical functions, following the same physical blueprint.
Riback’s lab developed a quantitative assay that confirmed these droplets are biophysically indistinguishable—akin to different soups simmering down to the same consistency. No matter which mutation initiated the process, each leukemia generated the same type of C-body.
"It was mind-blowing," Riback said. "All these distinct leukemia drivers, each with its unique molecular recipe, ended up creating the same droplet or condensate. That’s the common thread connecting these leukemias and it gives us a unified target. By understanding the biophysics of the C-body, we can figure out how to disrupt it and uncover new therapeutic strategies for multiple types of leukemia."
The team validated their findings across human cell lines, mouse models, and patient samples. When the researchers either genetically prevented the formation of these droplets or dissolved them with drugs, the leukemia cells stopped proliferating and began maturing into healthy blood cells.
"Seeing C-bodies in patient samples made the connection undeniable," said co-author Elmira Khabusheva, a postdoctoral associate in the Goodell lab. "Placing existing drugs in the context of C-bodies explains why they work across different leukemias and gives us a blueprint to design new therapies that specifically target the condensate. It's like finally seeing the forest instead of just individual trees."
"By pinpointing a shared nuclear structure that all these mutations rely on, we bridge basic biophysics with clinical leukemia," added Goodell. "This represents a fundamentally new way to think about therapy: target the structure itself."
"Across every model we examined, the pattern was unmistakable," said Datar. "Once we saw those bright dots, we knew we were witnessing something fundamental."
C-bodies give leukemia a tangible physical address—a structure scientists can now visualize, manipulate, and target. They offer a simple, physical explanation for how different mutations converge into the same disease and suggest treatment strategies aimed at dissolving the droplets that cancer depends on—similar to skimming fat off a soup to restore balance.
This discovery introduces a new paradigm for linking disease-driving droplets to common therapeutic targets. Just as distinct mutations in leukemia converge on the same condensate, other diseases, like ALS, may also form biophysically similar droplets governed by the same underlying physical rules.
Reference: Yau WYW, Kirn DR, Rabin JS, et al. Physical activity as a modifiable risk factor in preclinical Alzheimer’s disease. Nat Med. 2025. doi:10.1038/s41591-025-03955-6
This article is republished from Baylor College of Medicine materials (https://www.bcm.edu/news/scientists-uncover-nuclear-droplets-that-link-multiple-leukemias-revealing-new-therapeutic-target). Note: content may have been edited for length and clarity.
