Single-Cell Sequencing Analysis Reveals Cellular Dynamics Underlying Different Responses to Blinatumomab in Pediatric B-Cell Precursor Acute Lymphoblastic Leukemia

• Published in: Blood 2024-11, Vol.144, p.4214-4214
• Main Authors: Zhang, Mingying, Zhang, Yuanyuan, Qi, Peijing, Lin, Wei, Wu, Ying, Yu, Jiaole, Zheng, Huyong, Zhang, Ruidong
• Format: Article
• Language: English
• ISSN: 0006-4971
• DOI: 10.1182/blood-2024-204307

Introduction: Blinatumomab, a bispecific antibody that directs CD3 T cells to CD19 leukemic cells, shows promise in treating pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Samples for this study were obtained from children enrolled in an open-label, single-arm clinical trial (ChiCTR2400083570) that advances blinatumomab to the induction chemotherapy stage. Despite its potential, not all patients respond well to this treatment, making it crucial to elucidate the specific mechanisms underlying the varied responses to blinatumomab in BCP-ALL. Methods: Seven pediatric BCP-ALL patients with positive minimal residual disease (MRD, ≥1%) after 15 days of routine induction chemotherapy were included in our study and subsequently received a 28-day blinatumomab treatment. Bulk RNA-sequencing (RNA-seq) was used to determine the baseline cellular abundance of BCP-ALL. Single-cell RNA-sequencing (scRNA-seq) was performed to characterize the cellular dynamics of the B and T cells, as well as the B-cell and T-cell receptor (BCR/TCR) repertoires in BCP-ALL patients before, and on day 14 and 28 during blinatumomab treatment. Results: Among 7 patients, 2 patients (P-1 and P-2) remained MRD+ at all surveillance time points (insensitive group), while the other 5 patients achieved MRD- (MFC MRD