ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR282/070/SRR28244370/SRR28244370.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR282/068/SRR28244368/SRR28244368.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR282/074/SRR28244374/SRR28244374.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR282/075/SRR28244375/SRR28244375.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR282/071/SRR28244371/SRR28244371.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR282/067/SRR28244367/SRR28244367.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR282/072/SRR28244372/SRR28244372.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR282/066/SRR28244366/SRR28244366.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR282/073/SRR28244373/SRR28244373.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR282/069/SRR28244369/SRR28244369.fastq.gzprimaryOK200GenomicsLaboratory for Translational Cancer Immunology, LMU Gene Centerhttps://www.ebi.ac.uk/ena/browser/view/PRJNA1084808Homo sapiensxref:PubMed:39174782To date, bispecific antibodies designed to engage T cells have failed to show sustained responses in relapsed/refractory acute myeloid leukemia (R/R AML). Bispecific antibodies, including bispecific T-cell-engager (BiTE) molecules, predominantly recruit T cells from the local immune microenvironment. Because they are mainly applied in the R/R setting, understanding the fitness of T cells from bone marrow in AML progression, is fundamental for advancing this platform. Here, by flow cytometry analysis of bone marrow-derived T cells, we identified distinct differentiation stages and expression of inhibitory receptors at initial diagnosis (ID) and relapse (RL). Longitudinal transcriptional analyses of paired ID and RL T cells showed a senescent phenotype at ID, whereas an exhausted and memory phenotype was dominant at RL. In line with these observations, T cells at RL exhibited higher BiTE-mediated cytotoxicity than ID T cells. Finally, we provide evidence that T cells, both from ID and RL, exhibit limited functional capacity following continuous BiTE exposure compared to T cells from complete remission. Our study provides insights into the different stages of T-cell phenotype and function during AML evolution. Correlative biomarker studies in patients treated with T-cell-based immunotherapies are needed, to better understand resistance mechanisms and to advance the platform. Overall design: BMMCs from AML patients at time of initial diagnosis (ID) and relapse (RL) were retrospectively collected. Bone marrow CD3+ T cells from matched ID and RL samples as well as healthy donors (HD) were sorted and subjected to epigenome analysis.ENAfalseEvolution of T-Cell Fitness through AML Progression: Enhanced Bispecific T-Cell Engager-mediated Function of Bone Marrow T Cells at Remission Compared to Initial Diagnosis and Relapse [epigenome analysis]Evolution of T-Cell Fitness through AML Progression: Enhanced Bispecific T-Cell Engager-mediated Function of Bone Marrow T Cells at Remission Compared to Initial Diagnosis and Relapse [epigenome analysis]2025-09-242024-08-26PRJNA1084808GSE260999960639174782