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 documented. The CD44 adhesion molecule is strongly expressed on acute myeloid leukemia (AML) blasts. Using 2 myeloid cell lines, HL60 and NB4, evidence is presented that prior incubation with the CD44-specific monoclonal antibody (mAb) A3D8, reported to induce differentiation of AML blasts, significantly decreases apoptosis induced by 3 drugs used in AML chemotherapy: daunorubicin (DNR), mitoxantrone, and etoposide. In addition, in HL60 cells, CD44 ligation with A3D8 mAb fully abrogates the DNR-triggered generation of ceramide, a lipid second messenger involved in the DNR apoptotic signaling pathway. Moreover, results show that the A3D8 mAb and Bcl-2 additively inhibit DNR-induced apoptosis in HL60 cells overexpressing Bcl-2. These results suggest that, to eradicate AML blasts, the differentiation-inducing anti-CD44 mAb A3D8 should not be administered prior to apoptosis-inducing drugs.
Allouche
M
M
CNRS-UPCM, UPR2163, CHU Purpan, Toulouse, France. allouche@cict.fr
Charrad
R S
RS
Bettaieb
A
A
Greenland
C
C
Grignon
C
C
Smadja-Joffe
F
F
D017209:Apoptosis; D015815:Cell Adhesion Molecules; D006801:Humans; D018960:Hyaluronan Receptors; D007951:Leukemia, Myeloid / Q000276:immunology / Q000473:pathology*; D014407:Tumor Cells, Cultured
D015815:Cell Adhesion Molecules; D018960:Hyaluronan Receptors