Figure 8.

Proposed immune-evasion relapse mechanism in t(4;11) ALL

Upper panel: Scheme of ALL chemotherapy. Although complete remission (CR) is frequently achieved after induction therapy, relapse occurs prevalently during consolidation, reinduction, or maintenance phase. Bottom panel: Infant t(4;11) ALL cells characterized by low HOXA transcription overexpress IRX1, which in turn causes the upregulation of several EGR transcription factors. EGR3 was shown to cause the transcriptional upregulation of ICOSLG. The interaction of ICOSLG on ALL cells with ICOS on T-cells initiates the development of regulatory T-cells (T_regs). The accumulation of T_regs in the bone marrow niche could provide ALL cells with an immune privilege allowing them to acquire therapy resistance and to develop minimal residual disease (relapse).