Targeting the NOTCH1-MYC-CD44 axis in leukemia-initiating cells in T-ALL.

The NOTCH1-MYC-CD44 axis integrates cell-intrinsic and extrinsic signaling to ensure the persistence of leukemia-initiating cells (LICs) in T-cell acute lymphoblastic leukemia (T-ALL) but a common pathway to target this circuit is poorly defined. Bromodomain-containing protein 4 (BRD4) is implicated to have a role in the transcriptional regulation of oncogenes MYC and targets downstream of NOTCH1, and here we demonstrate its role in transcriptional regulation of CD44. Hence, targeting BRD4 will dismantle the NOTCH1-MYC-CD44 axis.