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cells, ball, cell, article, cart, therapy, fig, cdneg, google, scholar, tcdneg, supplementary, nature, expression, analysis, relapse, clusters, cas, data, leukemia, samples, acute, clones, tcdpos, pcr, antigen, lymphoblastic, mrna, singlecell, cancer, patient, leukemic, gene, cdna, genes, scrnaseq, med, chimeric, patients, anticd, treatment, car, tumoral, performed, information, study, genomics, umap, expressed, facs,

Topics {✒️}

org/cistarget/databases/homo_sapiens/hg19/refseq_r45/mc9nr/gene_based/hg19-tss-centered-10kb-7species hg19-tss-centered-10kb-7species nature portfolio org/record/4114854/files/refdata-cellranger-grch38-3 /supp/cell-exp/refdata-cellranger-grch38-3 privacy policy middle facs plots distinct anti-cd45-hashtag oligonucleotide advertising click chemistry tools social media regional council mrna library reads water 10 mm tco-peg4-nhs nature 545 nature specific anti-cd45-hto antibody future research reprints single-cell rna sequencing single-cell rna-sequencing acute lymphoblastic leukaemia libraries sequencing chimeric antigen receptor–modified research design research funding horizon 2020 research b-acute lymphoblastic leukemia bulk rna-sequencing data single-cell cdna synthesis dominique payet-bornet b-cell lymphoblastic leukemia express full-length transcripts 10 mm tco-peg4-nhs cancer-related childhood mortality1 investigate large-scale cnv peer review reports acute lymphoblastic leukemia 1 mm mtz-peg4-nhs evade cd19-targeted therapy cd19-negative relapse permitting de la sant� original author permissions chimeric antigen receptor libraries single-cell data escape car-mediated recognition /hoohm/cite-seq-count chimeric antigen receptors

Questions {❓}

• Which one is better for refractory/relapsed acute B-cell lymphoblastic leukemia: Single-target (CD19) or dual-target (tandem or sequential CD19/CD22) CAR T-cell therapy?
• Gov/sra?

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         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. CD19-negative relapses are observed in patients with B-cell acute lymphoblastic leukemia (B-ALL) treated with anti-CD19 CAR-T cells. Here, by single-cell RNA sequencing of leukemic cells in a patient with B-ALL, the authors show that pre-existing CD19 negative leukemic subclones are present before CAR-T cell therapy and can account for the relapse.
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      headline:Single-cell profiling identifies pre-existing CD19-negative subclones in a B-ALL patient with CD19-negative relapse after CAR-T therapy
      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. CD19-negative relapses are observed in patients with B-cell acute lymphoblastic leukemia (B-ALL) treated with anti-CD19 CAR-T cells. Here, by single-cell RNA sequencing of leukemic cells in a patient with B-ALL, the authors show that pre-existing CD19 negative leukemic subclones are present before CAR-T cell therapy and can account for the relapse.
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