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 p...

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Published inBlood Vol. 96; no. 3; pp. 1187 - 1190
Main Authors ALLOUCHE, M, RACHIDA SIHEM CHARRAD, BETTAIEB, A, GREENLAND, C, GRIGNON, C, SMADJA-JOFFE, F
Format Journal Article
LanguageEnglish
Published Washington, DC The Americain Society of Hematology 01.08.2000
Subjects
Antineoplastic agents
Apoptosis
Biological and medical sciences
Cell Adhesion Molecules
General aspects
Humans
Hyaluronan Receptors
Leukemia, Myeloid - immunology
Leukemia, Myeloid - pathology
Medical sciences
Pharmacology. Drug treatments
Tumor Cells, Cultured
Antineoplastic agent
Isomerases
Daunorubicin
Established cell line
Inhibition
Mitoxantrone
Antimitotic
Human
Promyelocytic leukemia
DNA topoisomerase (ATP-hydrolysing)
Anthraquinone derivatives
Enzyme
Acute
Cell adhesion molecule
Etoposide
Enzyme inhibitor
Malignant hemopathy
In vitro
HL60 cell line
Podophyllotoxine derivatives
Alkylating agent
Antibiotic
Antimetabolic
Cell death
Anthracyclins
Apoptosis
Acute myelocytic leukemia
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Summary: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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ISSN:0006-4971
1528-0020
DOI:10.1182/blood.V96.3.1187