An AACR-award-winning study opens new avenues for predicting therapeutic response in myelodysplastic syndromes
Dr. Manel Esteller, head of the Cancer Epigenetics group at the Institut de Recerca Sant Pau (IR Sant Pau), has been awarded by the American Association for Cancer Research (AACR) for the best article published in the last two years in Cancer Research Communications. The recognition highlights a study that provides a significant advance in understanding myelodysplastic syndromes and in predicting patient response to current treatments. The study was conducted during Dr. Esteller’s tenure at the Josep Carreras Leukaemia Research Institute (IJC).
“This recognition highlights not only the technological innovation of the study, but also its potential clinical impact in a patient group where there is still a major need to improve therapeutic outcomes,” says Dr. Manel Esteller.
The study focuses on myelodysplastic syndromes, a group of hematological disorders characterized by abnormal blood cell production and a risk of progression to acute leukemia. In these patients, hypomethylating agents—such as azacitidine—are the standard treatment, although approximately half of cases do not respond, significantly limiting clinical options.
The awarded work introduces an innovative approach based on single-cell technologies that allow simultaneous analysis, in each individual cell, of both genetic mutations and protein expression. This multi-omics strategy provides a much more precise view of tumor heterogeneity and disease evolution, overcoming the limitations of conventional analyses.
Single-cell analysis to understand the disease
Using this methodology, researchers were able to reconstruct in great detail the clonal architecture of the disease and its evolution before and after treatment, analyzing bone marrow samples from patients at different clinical stages. This approach made it possible to track different tumor cell populations—or clones—and identify how they change in response to therapy.
Unlike conventional analyses, which study cell populations in bulk, this technology allows the tumor to be broken down into its individual units and simultaneously characterizes genetic mutations and protein expression in each cell. This makes it possible not only to identify which alterations are present, but also in which cell types they appear and how they interact.
“Until now we analyzed the tumor as a whole, but this technology allows us to see what happens in each individual cell and understand how mutations and proteins interact in real time,” explains Dr. Manel Esteller. “This gives us a much more precise picture of the disease and its behavior.”
The results show that therapeutic response does not depend on a single genetic alteration, but on the combination of different cellular lineages and mutational profiles coexisting within the same patient. This integrated view helps identify complex biological patterns that were previously overlooked and are directly linked to disease evolution and treatment efficacy.
Key insights into treatment response prediction
In addition, the study demonstrates that patients who respond to treatment show a significant reduction in mutated cell clones after epigenetic therapy, whereas in non-responders these clones persist or even expand. This finding provides a solid biological basis for understanding why some patients benefit from treatment and others do not, opening the door to more personalized strategies.
“This knowledge allows us to start identifying which patients are more likely to respond before treatment begins,” notes Dr. Esteller. “It also helps us understand the mechanisms behind resistance, which is key for developing new therapeutic strategies.”
Furthermore, the results show that clonal heterogeneity is already present at diagnosis and that its evolution influences treatment efficacy. Tracking these changes at single-cell resolution also makes it possible to identify which cell populations persist after therapy and may drive treatment resistance.
Towards more personalized hematology
Beyond its methodological value, the study identifies potential response biomarkers and highlights new therapeutic vulnerabilities that could be targeted through drug combinations or precision therapies. Overall, the results suggest that integrated single-cell genetic and proteomic analysis could become a key tool for guiding clinical decision-making in these patients.
“The next step is to translate this type of analysis into clinical practice so we can make more informed and patient-specific therapeutic decisions,” concludes Dr. Esteller. “We are getting closer to truly personalized medicine in complex hematological diseases like this.”
This international recognition acknowledges both the technological innovation of the study and its potential clinical impact in a field where there is still a strong need to improve treatment selection and patient prognosis.
Reference article:
Campillo-Marcos I, Casado-Pelaez M, Davalos V, Ferrer G, Mata C, Mereu E, Roué G, Valcárcel D, Molero A, Zamora L, Xicoy B, Palomo L, Acha P, Manzanares A, Tobiasson M, Hellström-Lindberg E, Solé F, Esteller M. Single-cell multiomics analysis of myelodysplastic syndromes and clinical response to hypomethylating therapy. Cancer Res Commun 2024;4:365–77. https://doi.org/10.1158/2767-9764.CRC-23-0389.
