Figure 2.

Pre-B-cell-receptor signaling is regulated by a feed-back loop via Ikaros and Aiolos. The pre-B-cell-receptor (pre-BCR)-signaling cascade also involves FOXO transcription factors which may act as an interface between early B-cell development and FLT3-signaling that is frequently altered in acute myeloid leukemia (AML)[25]. FOXO-proteins are also regulated by downstream signaling of BCR-ABL1[27]. Disruption of Ikaros function by either deletions or protein interactions may interrupt the inhibitory feed-back loop to the pre-BCR pathway and thereby enhance pre-BCR-signaling.