Ligation of the CD44 adhesion molecule inhibits drug-induced apoptosis in human myeloid leukemia cells

Adhesion molecules can improve hematopoietic cell survival; however, their role in leukemic cell resistance to drug induced apoptosis is poorly docume nted. The CD44 adhesion molecule is strongly expressed on acute myeloid leu kemia (AML) blasts. Using 2 myeloid cell lines, HL60 and NB4, evidence is p resented that prior Incubation with the CD44-specific mono clonal antibody (mAb) A3D8, reported to induce differentiation of AML blasts, significantly decreases apoptosis induced by 3 drugs used in AML chemotherapy: daunorubi cin (DNR), mitoxantrone, and etoposide, In addition, in HL60 cells, CD44 li gation with A3D8 mAb fully abrogates the DNR-triggered generation of cerami de, a lipid second messenger involved in the DNR apoptotic signaling pathwa y. Moreover, results show that the A3D8 mAb and Bcl-2 additively inhibit DN R-induced apoptosis in HL60 cells overexpressing Bcl-2, These results sugge st that, to eradicate AML blasts, the differentiation-inducing anti-CD44 mA b A3D8 should not be administered prior to apoptosis-inducing drugs. (C) 20 00 by The American Society of Hematology.