Figure 5. Model of UHRF1-ROR1 regulatory mechanism.
The 1;19 fusion product leads to cell arrest and constitutively active pre-BCR signaling (top). This signaling can be suppressed by small-molecule inhibitors, such as dasatinib, but kinase inhibition is rescued by increased ROR1 expression (middle). Targeting the UHRF1-ROR1 mechanism with compounds such as naphthazarin can suppress baseline ROR1 levels. In combination with pre-BCR inhibition (via dasatinib), naphthazarin helps to prevent upregulation of ROR1 to maximize t(1;19) pre B-ALL apoptotic cell death (bottom).