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.

CD44 ligation induces caspase-independent cell death via a novel calpain/AIF pathway in human erythroleukemia cells.

Ligation of the cell surface molecule CD44 by anti-CD44 monoclonal antibodies (mAbs) has been shown to induce cell differentiation, cell growth inhibition and in some cases, apoptosis in myeloid leukemic cells. We report, herein, that exposure of human erythroleukemic HEL cells to the anti-CD44 mAb A3D8 resulted in cell growth inhibition followed by caspase-independent apoptosis-like cell death. This process was associated with the disruption of mitochondrial membrane potential (Delta Psi m), the mitochondrial release of apoptosis-inducing factor (AIF), but not of cytochrome c, and the nuclear translocation of AIF.

CD44 ligation induces apoptosis via caspase- and serine protease-dependent pathways in acute promyelocytic leukemia cells.

We have recently reported that ligation of the CD44 cell surface antigen with A3D8 monoclonal antibody (mAb) triggers incomplete differentiation and apoptosis of the acute promyelocytic leukemia (APL)-derived NB4 cells. The present study characterizes the mechanisms underlying the apoptotic effect of A3D8 in NB4 cells. We show that A3D8 induces activation of both initiator caspase-8 and -9 and effector caspase-3 and -7 but only inhibition of caspase-3/7 and caspase-8 reduces A3D8-induced apoptosis.