Elucidating minimal residual disease of paediatric B-cell acute lymphoblastic leukaemia by single-cell analysis
Menée in vitro et in vivo, cette étude analyse, au diagnostic, au stade résiduel et à la récidive, le profil transcriptomique de lymphocytes B de leucémies lymphoblastiques aiguës puis met en évidence l'intérêt d'inhiber la voie de l'hypoxie pour sensibiliser les cellules leucémiques à la chimiothérapie
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.
Nature Cell Biology 2022