Elucidating minimal residual disease of paediatric B-cell acute lymphoblastic leukaemia by single-cell analysis

Zhang et al. perform single-cell RNA and B-cell receptor sequencing to characterize the transcriptomic profiles of B-cell acute lymphoblastic leukaemia cells at diagnosis, residual and relapse stages, uncovering the hypoxia pathway as a potential target for residual leukaemia cells. Minimal residual disease that persists after chemotherapy is the most valuable prognostic marker for haematological malignancies and solid cancers. Unfortunately, our understanding of the resistance elicited in minimal residual disease is limited due to the rarity and heterogeneity of the residual cells. Here we generated 161,986 single-cell transcriptomes to analyse the dynamic changes of B-cell acute lymphoblastic leukaemia (B-ALL) at diagnosis, residual and relapse by combining single-cell RNA sequencing and B-cell-receptor sequencing. In contrast to those at diagnosis, the leukaemic cells at relapse tended to shift to poorly differentiated states, whereas the changes in the residual cells were more complicated. Differential analyses highlighted the activation of the hypoxia pathway in residual cells, resistant clones and B-ALL with MLL rearrangement. Both in vitro and in vivo models demonstrated that inhibition of the hypoxia pathway sensitized leukaemic cells to chemotherapy. This single-cell analysis of minimal residual disease opens up an avenue for the identification of potent treatment opportunities for B-ALL.

Automated summary

In this study, Zhang et al. used single-cell transcriptomics and B-cell receptor sequencing to analyze the transcriptomic profiles of B-cell acute lymphoblastic leukaemia cells at diagnosis, residual, and relapse stages. They found that the hypoxia pathway could be a potential target for residual leukaemia cells.