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Blood, Vol. 96 No. 3 (August 1), 2000:
pp. 1187-1190
BRIEF REPORT
Ligation of the CD44 adhesion molecule inhibits drug-induced
apoptosis in human myeloid leukemia cells
Michèle Allouche,
Rachida Sihem Charrad,
Ali Bettaieb,
Catherine Greenland,
Cécile Grignon, and
Florence Smadja-Joffe
From CNRS-UPCM, UPR2163, CHU Purpan, Toulouse, France; INSERM U268,
Hopital Paul Brousse, Villejuif, France; CJF INSERM 9503, Centre
Claudius Regaud, Toulouse, France; INSERM U517, Faculté de
Médecine et Pharmacie, Dijon, France
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.
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