Leukemia genomics expert Charles G. Mullighan, MBBS (Hons), MSc, MD, FRS, will deliver the plenary “Genomics and Futures of Personalized Therapy in ALL” at 1:05 p.m. on September 5, 2025 at the Thirteenth Annual Meeting of the Society of Hematologic Oncology.
Dr. Mullighan is the senior deputy director at the St. Jude Children’s Research Hospital Comprehensive Cancer Center in Memphis, Tennessee, and was recently elected a Fellow of the Royal Society of London, the 364-year-old scientific academy that once counted Sir Isaac Newton and Benjamin Franklin among its members.
“This was an unexpected and tremendous honor,” he told SOHO Insider. “It recognizes the work our leukemia team at St. Jude and our collaborators have done over the past two decades and the insights it has given us into the disease, its biology, and its clinical implications.”
Dr. Mullighan was elected to the Royal Society in recognition of his trailblazing contributions to genomic research, which have advanced the understanding, diagnosis, and treatment of acute leukemia, notably childhood acute lymphoblastic leukemia (ALL). His studies have redefined the disease by identifying novel subtypes, uncovering critical genomic drivers, and advancing precision medicine approaches.
“The extensive work of Dr. Mullighan was critical in deciphering the personal biology of the disease and therefore in improving outcomes,” Elias Jabbour, MD, professor in the Department of Leukemia at the University of Texas MD Anderson Cancer Center in Houston, said in an interview with SOHO Insider.
Dr. Jabbour, who will be introducing Dr. Mullighan, added, “Dr. Mullighan’s work was the foundation of so many clinical trials now taking place.”
Although Dr. Mullighan trained as an adult hematologist, in his position at St. Jude Children’s Research Hospital, he has focused on how different age groups acquire different genetic changes in leukemia and how the genomic landscape varies across the age spectrum.
“Looking at this information over time is very important for the adult setting,” he said. “It tells us what the genetic interactions are in a cohort and determines, for example, whether patients could get to randomization and get benefit or not, whether they will respond or not.”
Asked how his understanding of leukemia has changed since he first entered the field, Dr. Mullighan cited “a much more detailed and nuanced understanding of the genetic basis of the acute leukemias, particularly ALL.”
“We understand more of the subgroups of the disease and the constellations of genetic changes that define them,” he said. “We have a much more detailed understanding of the genetic determinants of whether a patient responds to treatment or not, and the specific genetic changes that are associated with very high-risk disease that have therapeutic implications.”
Dr. Mullighan also cited progress in less common and less well studied leukemias, including T-lineage and lineage ambiguous leukemias.
“These are genetically more complex and challenging to understand, but recent work has given us a greater understanding of their genetic basis and more insights into how genetic drivers and the cell of origin interact to determine the nature of the disease,” he said.
Now that the field has achieved what he characterizes as a “near complete understanding” of the genetic drivers of the disease, Dr. Mullighan said he expects a number of new opportunities to open up.
“I think we’re poised to develop experimental models through genome editing and other approaches,” he said. “We’re also using our experience from understanding genetic approaches to look at newer approaches to context of treatment and drug development, including immunotherapies and targeted protein degradation.”
The hope is that genomic information will help lead to not only better treatments for high-risk disease, but also insights into which patients are likely to respond well and potentially benefit from de-escalation of treatment while still achieving the desired therapeutic effect.
Studying the role of genomic information in the context of newer immunotherapies has reinforced the point that “these treatments are not a panacea,” Dr. Mullighan said. “They’re wonderful, but they don’t work for everyone, and we still have a lot of work to do, particularly in the highest risk subsets of disease.”
Noting the increasingly small subsets of disease for which a given therapy might be attractive, Dr. Mullighan called for “a more facile clinical trial structure,” identifying this as a challenge facing the field.
“The trials can’t be the same as they used to be, where we had hundreds of patients over a long period of time, essentially treated in the same way with some variation,” he said. “There’s clearly a need now to have a more reactive approach that can tailor therapy more quickly where it’s needed for small subtypes of disease.”
Asked what drives his research, Dr. Mullighan said, “ultimately, a lot of what drives me and drives the work we do here is not just doing the genetic profiling, but taking that information as a starting point to then develop better models of the disease to give us better understanding of the actual biological basis of what these genetic changes do, not just what they are, but how they act.”
“Periodically we have these almost seismic shifts in treatment, as we’ve seen with chimeric antigen receptor (CAR)-T a few years ago now,” he added. “One can, I guess, be seduced by them, understandably, and perhaps lose a focus on some of the biology,” he said.
He also stressed the importance of translating research results into practical application at the clinical level.
“I think we have a lot to do there still, but we have had some success in translating a lot of this information into data diagnostic approaches and also, in some settings, therapeutic approaches as well,” he said. “We’ve had a number of studies where we’ve looked at how genetic information influences our understanding of response to monoclonal antibodies and now CAR T-cell therapy.”
As an example of the translation of data diagnostic approaches to clinical settings, he cites the rapid spread of deployment of RNA sequencing approaches, which he notes “don’t give all the information, but they certainly give a lot and that that is becoming easier as well.”
Many of Dr. Mullighan’s landmark studies on genetically more complex disease subsets, such as T-lineage leukemia, were based on whole genome DNA sequencing, which is challenging to implement in a clinical setting.
“That remains a challenge, and in fact we have a very active program now trying to strip down the approaches to make them as simple as possible without compromising delivery of information to enable the deployment of tools in the clinic,” he said. “It’s not so much of a technological barrier; it’s more of an informatics and speed barrier—but those barriers are being dismantled.”
In addition to his leadership role in the St. Jude Comprehensive Cancer Center, Dr. Mullighan is also divisional director for research in the Department of Pathology, director of the Center of Excellence for Leukemia Studies, and the William E. Evans Endowed Chair. He also serves on the SOHO Steering Committee.
Visit the SOHO 2025 meeting news page for more coverage from the meeting.
