CD44 activation enhances acute monoblastic leukemia cell survival via Mcl-1 upregulation.

Survival of acute myeloid leukemia (AML) cells is regulated by their adherence to bone marrow stromal environment. Several adhesion molecules mediate interactions between AML cells and stroma, but their specific role in AML cell survival is still poorly understood. Here, we show that CD44 activation with the Hermes-3 monoclonal antibody enhances primary AML5 blast survival and increases apoptosis resistance of THP-1 monoblastic leukemia cells. Moreover, we show that CD44 activation upregulates the anti-apoptotic Mcl-1 protein and that Mcl-1 is essential for apoptosis resistance of THP-1 cells. These results suggest that Mcl-1 inhibitors might be required to block pro-survival activity of CD44 in AML5.