scRNA-seq reveals an immune microenvironment and JUN-mediated NK cell exhaustion in relapsed T-ALL

T-cell acute lymphoblastic leukemia (T-ALL) is a heterogeneous disease characterized with high relapse rate. By single-cell transcriptome analysis, we characterized the bone marrow immune microenvironment in T-ALL patients, identifying 13 major cell clusters. These patients exhibited abnormally expanded HSCs and GMPs, immunosuppressive traits in CD4+T, CD8+T, and NK cells. Subdividing CD4+T cells revealed two subsets transitioning between Th1/Th2, ANXA1-GATA3-CD4+T and ANXA1+GATA3+CD4+T. Additionally, NK cells demonstrated exhaustion in the tumor microenvironment of relapse T-ALL patients, with JUN identified as a critical factor. Additionally, JUN was also highly expressed in T-ALL and was crucial for maintaining its proliferation. The JUN inhibitor exhibited successful lethality toward leukemia cells and ameliorate NK cell exhaustion in relapse T-ALL cell line, as well as in CDX, PDX, and NOTCH1 mutant mouse models. In summary, our findings enhance the understandin..., , , # scRNA-seq reveals an immune microenvironment and JUN-mediated NK cell exhaustion in relapsed T-ALL

## Description of the data and file structure

This dataset includes single-cell transcriptome sequencing data from 3 normal donors, 3 primary T-ALL patients, and 3 relapsed T-ALL patients. It also includes single-cell transcriptome sequencing technology of T-ALL PDX model mice on days 7, 12, and 21 to simulate the disease states of primary, remission, and relapse. Finally, the dataset also includes RNA-seq data of the JNK-IN-8 treatment group and the control group in the T-ALL NOTCH1 gene mutation mouse model.

## Code/software

**Data quality control**

To transform the original BCL files into FASTQ format, the application 10xGenomics Cell Ranger (version 3.1.0) was employed. Following that, this format was utilized for alignment and count quantification. Prior to mapping to the reference genome, all readings were examined for unique molecular identifiers (UMIs) or low-quality barcode...,