IFITM3P6 and FLT3LG activate T cells in the tumor microenvironment and are prognostic factors in acute myelocytic leukemia

The CIBERSORT algorithm and
weighted gene co-expression network analysis (WGCNA) were utilized to identify
genes that are significantly associated with certain immune cells. Cox regression
analyses were introduced to screen overall survival-related genes. Then the
ESTIMATE scoring method and single-sample gene set enrichment analysis (ssGSEA)
studies were used to group the immune activity of the tumor microenvironment (TME)
and analyze the correlation between the critical genes and immune activity.
Single-cell transcriptome analyses were used to define the immune cell that
highly enriched these genes. Consequently,<b>
</b>IFITM3P6 and FLT3LG were significantly associated with the OS rate and were
important in the activation of CD8+ and CD4+ T cells. Moreover, they were
positively correlated with immune activity activation. Reduced DNA methylation
of FLT3 induced its ectopic expression in progenitor cells and tumor cells and
downregulation in dendritic cells, diminishing stimulatory signals from
dendritic cells to T cells through the FLT3-FLT3LG axis. In addition, increased
N⁶-methyladenosine (m6A) RNA modulation
downregulated the expression of IFITM3P6, which consequently induced the downregulation
of CBX7 via the IFITM3P6-miR-6748-3p-CBX7 axis, leading to the apoptosis of T
cells. Finally, correlation analysis and protein-protein affinity analysis
suggested FLT3LG and IFITM3P6 may synergistically activate T cells by
NOTCH1-MAML2-CBX7 suppressive complex.<b></b>