Single-cell RNA sequencing reveals chemotherapy-induced apoptosis in acute myeloid leukemia via B cell depletion and M2 to M1 macrophage repolarization.

PURPOSE: This study aimed to investigate the dynamic changes of immune microenvironment in acute myeloid leukemia (AML) during chemotherapy, thereby, exploring the mechanism of chemotherapy resistance of AML.

METHODS

Single cell RNA sequencing (scRNAseq) was performed on 6 bone marrow samples from AML before or after chemotherapy (BC, AC) to obtain the fastq files. Bioinformatics analysis including GSEA, GSVA, pseudotime trajectory and cell chat analysis was used for constructing single-cell transcriptome and observing the dynamic changes of immune microenvironment. Western blot was carried out for validation.

RESULTS

A total of 11 cell subpopulations were obtained, among which B cells, HSCs, and TAMs were the significant changed between BC and AC groups. MCM7 gene was highly expressed in malignant cells, co-expressed with CD34 + pre B cells in BC groups, and decreased in AC group. The SPINK2 + B cells activated JAK-STAT pathway. Furthermore, we found that chemotherapy driven the transition for M2 to M1 in TAMs polarization.

CONCLUSIONS

MCM7 and SPINK2 were the targeted genes in AML during chemotherapy, which help for providing a theoretical basis for combined immunotherapy/targeted-therapy strategies.