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Single-cell profiling identifies pre-existing CD19-negative subclones in a B-ALL patient with CD19-negative relapse after CAR-T therapy

ABSTRACT: Single-cell profiling identifies pre-existing CD19-negative subclones in a B-ALL patient with CD19-negative relapse after CAR-T therapy

PROVIDER: PRJNA643723 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12135757_1.fastq.gz	Fastqsanger.gz
	SRR12135757_2.fastq.gz	Fastqsanger.gz
	SRR12135758_1.fastq.gz	Fastqsanger.gz
	SRR12135758_2.fastq.gz	Fastqsanger.gz

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Single-cell profiling identifies pre-existing CD19-negative subclones in a B-ALL patient with CD19-negative relapse after CAR-T therapy

Project description:Chimeric antigen receptor T cell (CAR-T) targeting the CD19 antigen represents an innovative therapeutic approach to improve the outcome of relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL). Yet, despite a high initial remission rate, CAR-T therapy ultimately fails for some patients. Notably, around half of relapsing patients develop CD19 negative (CD19neg) B-ALL allowing leukemic cells to evade CD19-targeted therapy. Herein, we investigate leukemic cells of a relapsing B-ALL patient, at two-time points: before (T1) and after (T2) anti-CD19 CAR-T treatment. We show that at T2, the B-ALL relapse is CD19 negative due to the expression of a non-functional CD19 transcript retaining intron 2. Then, using single-cell RNA sequencing (scRNAseq) approach, we demonstrate that CD19neg leukemic cells were present before CAR-T cell therapy and thus that the relapse results from the selection of these rare CD19neg B-ALL clones. In conclusion, our study shows that scRNAseq profiling can reveal pre-existing CD19neg subclones, raising the possibility to assess the risk of targeted therapy failure.

2020-12-11 | GSE153697 | GEO

Single-cell profiling identifies pre-existing CD19-negative subclones in a B-ALL patient with CD19-negative relapse after CAR-T therapy.

| S-EPMC7870924 | biostudies-literature

Cd19

Project description:Rattus norvegicus Cd19, CD19 molecule [Source:RGD Symbol;Acc:1309086], is expressed in 3 baseline experiment(s);

| ENSRNOG00000018311 | ExpressionAtlas

CD19

Project description:Sus scrofa CD19, CD19 molecule [Source:VGNC Symbol;Acc:VGNC:86393], is differentially expressed in 2 experiment(s);

| ENSSSCG00000007807 | ExpressionAtlas

Cd19

Project description:Mus musculus Cd19, CD19 antigen [Source:MGI Symbol;Acc:MGI:88319], is differentially expressed in 63 experiment(s);

| ENSMUSG00000030724 | ExpressionAtlas

CD19

Project description:Oryctolagus cuniculus CD19, CD19 molecule [Source:HGNC Symbol;Acc:HGNC:1633], is expressed in 1 baseline experiment(s);

| ENSOCUG00000026150 | ExpressionAtlas

CD19

Project description:Homo sapiens CD19, CD19 molecule [Source:HGNC Symbol;Acc:HGNC:1633], is expressed in 31 baseline experiment(s);

| ENSG00000177455 | ExpressionAtlas

CD19

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| ENSSSCG00000007807 | ExpressionAtlas

CD19

Project description:Macaca mulatta CD19, CD19 molecule [Source:VGNC Symbol;Acc:VGNC:70754], is expressed in 1 baseline experiment(s);

| ENSMMUG00000006880 | ExpressionAtlas

CD19

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