NOTCH signaling roles in acute myeloid leukemia cell growth and interaction with other stemness-related signals.

NOTCH activation plays oncogenic roles in acute T-lymphoblastic leukaemia (T-ALL). However, whether NOTCH is oncogenic or tumor-suppressive in acute myeloid leukaemia (AML) is still controversial. Herein, the roles of NOTCH in AML are reviewed. AML cells express NOTCH and NOTCH ligands; however, cell-autonomous activation is not observed. Activating NOTCH1 mutations are rare in AML, unlike in T-ALL. NOTCH ligand stimulation generally suppresses the in vitro growth of AML cells but promotes transient growth of some samples. Conversely, knockdown of NOTCH1 and NOTCH2 does not affect the growth of AML cells, whereas it suppresses the growth of T-ALL cells. These findings suggest that NOTCH is dispensable or suppressive for AML cell growth. However, the effects of NOTCH differ depending on cell conditions, and various stemness-related signals modify these effects; hence, forced NOTCH activation in vitro may not exhibit effects in bone marrow. Thus, further understanding is required for the development of AML therapies targeting NOTCH signalling.