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ISAL 2025 | Dissecting the heterogeneity within AML with myelodysplasia-related gene mutations
Albert Cortés-Bullich, MD, Hospital Clinic of Barcelona, Barcelona, Spain, discusses a study using RNA-seq analysis to dissect the heterogeneity within acute myeloid leukemia (AML) with myelodysplasia-related gene mutations. He highlights that this analysis revealed three prognostic subgroups, with one subgroup enriched in lymphocytes, which correlated with better outcomes, and another subgroup enriched in monocytes and neutrophils, which performed poorly. Dr Cortés-Bullich suggests different therapeutic options dependent on the subgroup, but further research is required to make conclusions. This interview took place at the 19th International Symposium on Acute Leukemias (ISAL XIX) in Munich, Germany.
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Transcript
So we wanted to try to dissect the heterogeneity within this group with AML with myelodysplasia-related gene mutations. This is a heterogeneous group and we wanted to try to find subgroups of prognostic impact within this group. We performed RNA-seq, bulk RNA-seq, on 50 patients with this diagnosis and we did unsupervised clustering that revealed three different groups. One of them was enriched in lymphocytes, another group was enriched in monocytes and macrophages, and there was the third group which didn’t have any special enrichment...
So we wanted to try to dissect the heterogeneity within this group with AML with myelodysplasia-related gene mutations. This is a heterogeneous group and we wanted to try to find subgroups of prognostic impact within this group. We performed RNA-seq, bulk RNA-seq, on 50 patients with this diagnosis and we did unsupervised clustering that revealed three different groups. One of them was enriched in lymphocytes, another group was enriched in monocytes and macrophages, and there was the third group which didn’t have any special enrichment. The data we collected from RNA-seq correlated with cytology on diagnosis. What we found is that the group enriched in lymphocytes didn’t have any mutation in splicing genes. What we also found is that these lymphocytes were mainly CD8 central memory, effector memory lymphocytes. Also, we found that neutrophils were more frequently overrepresented in this group. And in this group, enriched lymphocytes, they did perform better than the rest. They had within the reach of overall survival of these patients, and that was because of better progression-free survival. On the other hand, patients with monocyte and neutrophil enrichment, they performed very badly. We think this might shed some light or we could try to dissect this information upon diagnosis. We could try to better define these patients that will benefit from allogeneic stem cell transplantation. The group that didn’t perform well, they don’t benefit from allogeneic stem cell transplantation. We just think that if we are able to further prove these differences in tumor microenvironment would be interesting in the future. Also, this group that performs better, that has an enriched microenvironment with lymphocytes, maybe this group does better when we use immunotherapy, we don’t know. It’s interesting for us to keep studying that.
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