ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR282/084/SRR28244384/SRR28244384_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR282/080/SRR28244380/SRR28244380_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR282/082/SRR28244382/SRR28244382_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR282/081/SRR28244381/SRR28244381_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR282/085/SRR28244385/SRR28244385_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR282/078/SRR28244378/SRR28244378_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR282/091/SRR28244391/SRR28244391_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR282/085/SRR28244385/SRR28244385_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR282/080/SRR28244380/SRR28244380_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR282/083/SRR28244383/SRR28244383_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR282/088/SRR28244388/SRR28244388_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR282/089/SRR28244389/SRR28244389_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR282/086/SRR28244386/SRR28244386_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR282/079/SRR28244379/SRR28244379_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR282/077/SRR28244377/SRR28244377_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR282/076/SRR28244376/SRR28244376_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR282/082/SRR28244382/SRR28244382_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR282/078/SRR28244378/SRR28244378_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR282/086/SRR28244386/SRR28244386_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR282/084/SRR28244384/SRR28244384_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR282/076/SRR28244376/SRR28244376_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR282/079/SRR28244379/SRR28244379_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR282/088/SRR28244388/SRR28244388_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR282/087/SRR28244387/SRR28244387_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR282/091/SRR28244391/SRR28244391_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR282/090/SRR28244390/SRR28244390_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR282/081/SRR28244381/SRR28244381_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR282/077/SRR28244377/SRR28244377_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR282/087/SRR28244387/SRR28244387_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR282/083/SRR28244383/SRR28244383_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR282/089/SRR28244389/SRR28244389_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR282/090/SRR28244390/SRR28244390_2.fastq.gzprimaryOK200GenomicsLaboratory for Translational Cancer Immunology, LMU Gene Centerhttps://www.ebi.ac.uk/ena/browser/view/PRJNA1084807Homo sapiensTo 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 transcriptome analysis.xref:PubMed:39174782ENAfalseEvolution 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 [transcriptome 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 [transcriptome analysis]2025-09-242024-08-26PRJNA1084807GSE261000960639174782