Researchers have identified two distinct immune-based subgroups within acute myeloid leukemia (AML) that exhibit different immune infiltration patterns, mutational landscapes, and drug sensitivities, offering new insights into prognosis and treatment strategies. The study, published in Frontiers in Immunology, highlights the potential for precision medicine approaches in AML by refining risk stratification based on immune characteristics.
The research team conducted integrated analyses of multiple sequencing datasets from AML patients to assess the immune landscape. Using various algorithms, they estimated immune infiltration in AML samples and developed a subgroup prediction model. This model identified two subgroups, designated G1 and G2, with significantly different immune profiles.
The G1 subgroup was characterized by higher immune infiltration, a more monocytic phenotype, and increased proportions of monocytes/macrophages. It also showed higher frequencies of FLT3, DNMT3A, and NPM1 mutations. Notably, the G1 subgroup was associated with a poorer prognosis and lower T cell infiltration score (TIS) compared to G2.
"Our study enriches the current AML risk stratification and provides guidance for precision medicine in AML," the authors stated.
Further analysis revealed differential expression of T-cell-based immunotherapy target antigens between the subgroups. Antigens such as CLEC12A, Folate receptor β, IL1RAP, and TIM3 were more highly expressed in G1, while CD117, CD244, CD96, WT1, and TERT showed higher expression in G2. These findings suggest potential targets for subgroup-specific immunotherapies.
In terms of drug sensitivity, G1 samples demonstrated higher sensitivity to elesclomol and panobinostat but increased resistance to venetoclax compared to G2 samples. The researchers also observed correlations between immune infiltration and drug resistance, with higher immune infiltration correlating with resistance to elesclomol and panobinostat but sensitivity to venetoclax.
Implications for Treatment
These findings have significant implications for the treatment of AML. By identifying immune-based subgroups with distinct characteristics, clinicians can potentially tailor treatment strategies to improve outcomes. For example, patients in the G1 subgroup may benefit from therapies targeting specific antigens or from alternative treatment regimens that overcome venetoclax resistance.
The study underscores the importance of considering the immune landscape in AML and highlights the potential for precision medicine approaches to improve patient outcomes. Further research is needed to validate these findings and to develop targeted therapies based on immune-based subgroups.
