Single-cell proteogenomic analysis of clonal evolution in PDX models of AML treated with IDH inhibitors.

ABSTRACT: Clonal heterogeneity in acute myeloid leukemia (AML) can drive drug resistance because different clones may respond variably to treatments. Studying the evolution of these clones under the influence of therapeutic selective pressures is important for designing strategies to overcome drug resistance. Here, we used single-cell proteogenomic analysis to monitor the clonal evolution and differentiation of isocitrate dehydrogenase (IDH)-mutated AML in patient-derived xenografts (PDX) treated with IDH inhibitors alone or in combination with other antileukemic therapies. Furthermore, we generated mixed PDX models by coengrafting ≥2 leukemic samples into the same animal and used single-cell DNA sequencing to deconvolute their clonal composition. Using these models, we tracked clonal evoluti

SUBMITTER: Liu ACH 

PROVIDER: S-EPMC12820584 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature