Studies by an international team of researchers headed by investigators in the labs of Margaret Goodell, PhD, and Joshua Riback, PhD, at Baylor College of Medicine, suggest that a hidden structure inside the cell may rewrite how scientists understand leukemia. The scientists’ preclinical research indicated that different genetic drivers of leukemia use the same secret compartments—known as C-bodies—inside the cell nucleus to keep cancer growing.
The studies involved in vitro tests and in vivo experiments in models of acute myeloid leukemia (AML) characterized by mutant NPM1 (NPM1c). The results point to a shared physical target that could inspire new kinds of treatments. The researchers say their work reshapes a long-standing view of how a common leukemia begins and offers a fresh way to design therapies that strike a single weakness shared across distinct genetic forms of the disease. Goodell said, “By identifying a shared nuclear structure that all these mutations depend on, we connect basic biophysics to clinical leukemia. It means we can target the structure itself—a new way of thinking about therapy.”
The team’s findings are described in Cell, in a paper titled “Disparate leukemia mutations converge on nuclear phase-separated condensates,” in which the researchers stated “In this study, we show that NPM1c forms phase-separated nuclear condensates—termed coordinating bodies or C-bodies—across multiple models of NPM1-mutant AML.” They concluded that their collective data “… establish C-bodies as a therapeutic vulnerability in leukemia.”
Leukemia starts when mutations in blood-forming cells disrupt the balance between growth and differentiation. Patients with entirely different genetic changes show strikingly similar patterns of gene activity and can respond to the same drugs. What invisible thread could make so many mutations behave the same way?
To find out, the Riback and Goodell labs at Baylor joined forces. Riback, an assistant professor and CPRIT Scholar who studies how proteins form droplets through a process known as phase separation, teamed with Goodell, Baylor’s chair of Molecular and Cellular Biology, and a pioneer in understanding how blood stem cells give rise to leukemia. Together, they set out to follow the physics hidden inside cancer’s chemistry.
The researchers suggest that a moment of clarity came when graduate student and first author, Gandhar Datar, who is co-mentored by Riback and Goodell, peered into Riback’s high-resolution microscope and saw something that no one expected: leukemia cell nuclei shimmered with a dozen bright dots—tiny beacons missing from healthy cells.
Further investigation found that those dots weren’t random, they were new nuclear compartments formed by phase separation, the same physical principle that describes why oil droplets form in water. “Condensates are liquid-like phases with physics similar to oil separating from water but with substantially higher complexity,” the investigators explained.
They named the new compartments “coordinating bodies,” or C-bodies. These compartments contained large amounts of mutant leukemia proteins and drew in many normal cell proteins to coordinate activation of the leukemia program. “Our data demonstrate that C-bodies enrich proteins that facilitate leukemogenesis,” they noted.
The team found that inside the cell nucleus the C-bodies act like miniature control rooms, pulling together the molecules that keep leukemia genes switched on. Like drops of oil collecting on the surface of soup, they appear when the cell’s molecular ingredients reach just the right balance.
Even more surprising, the study indicated that cells carrying entirely different leukemia mutations formed droplets with the same behavior. Although their chemistry differs, the resulting nuclear condensates perform the same function, using the same physical playbook.
A new quantitative assay developed in the Riback lab confirmed this. These droplets are biophysically indistinguishable—like soups made from different ingredients that still simmer into the same consistency. No matter which mutation started the process, each leukemia formed the same kind of C-body.
“It was astonishing,” Riback said. “All these different leukemia drivers, each with its own recipe, ended up cooking the same droplet, or condensate. That’s what unites these leukemias and gives us a common target. If we understand the biophysics of the C-body, its general recipe, we’ll know how to dissolve it and reveal new insights for targeting many leukemias.”
The team confirmed their finding across human cell lines, mouse models, and patient samples. “Here, we show for the first time that NPM1c forms C-bodies, a new condensate observed across in vitro and in vivo models of NPM1-mutant AML, and multiple primary NPM1-mutant AML patient samples,” the scientists wrote. Datar further commented, “Across every model we studied, the pattern was the same. Once we saw those bright dots, we knew we were looking at something fundamental.” When the investigators then tweaked the proteins so they could no longer form these droplets—or dissolved them with drugs—the leukemia cells stopped dividing and began to mature into healthy blood cells.
“Seeing C-bodies in patient samples made the link crystal clear,” said co-author Elmira Khabusheva, PhD, a postdoctoral associate in the Goodell lab. “By putting existing drugs into the context of the C-body, we can see why they work across different leukemias and start designing new ones that target the condensate itself. It’s like finally seeing the whole forest instead of just the trees.”
The discovery of C-bodies gives leukemia a physical address, a structure scientists can now see, touch, and target. It provides a simple physical explanation for how different mutations converge on the same disease and points to treatments aimed at dissolving the droplets that cancer depends on—like skimming the fat from a soup to restore its balance. “Together, these data define a new condensate that we term the coordinating body (C-body) and establish C-bodies as a therapeutic vulnerability in leukemia,” the researchers concluded. “Our data demonstrate C-bodies are necessary for all hallmarks of this disease: maintaining leukemic gene expression, preventing differentiation, and promoting expansion in vivo.”
The findings set up a new paradigm for linking droplet-forming disease drivers into shared, generalizable therapeutic targets, revealing that just as distinct mutations in leukemia converge on the same condensate, other diseases, such as ALS, may each assemble their own biophysically indistinguishable droplets governed by the same physical rules.