Ligation of the CD44 adhesion molecule inhibits drug-induced apoptosis in human myeloid leukemia cells
Autor: | Rachida Sihem Charrad, Catherine Greenland, Ali Bettaieb, Michèle Allouche, Florence Smadja-Joffe, Cécile Grignon |
---|---|
Rok vydání: | 2000 |
Předmět: |
Programmed cell death
Myeloid HL60 Daunorubicin Immunology Apoptosis Biochemistry chemistry.chemical_compound hemic and lymphatic diseases medicine Tumor Cells Cultured Humans biology Cell adhesion molecule CD44 Myeloid leukemia Cell Biology Hematology medicine.anatomical_structure Hyaluronan Receptors chemistry Leukemia Myeloid biology.protein Cancer research Apoptotic signaling pathway Cell Adhesion Molecules medicine.drug |
Zdroj: | Europe PubMed Central |
ISSN: | 0006-4971 |
Popis: | 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. |
Databáze: | OpenAIRE |
Externí odkaz: |