Back to Search
Start Over
Ligation of the CD44 adhesion molecule inhibits drug-induced apoptosis in human myeloid leukemia cells
- Source :
- Europe PubMed Central
- Publication Year :
- 2000
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 00064971
- Volume :
- 96
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Blood
- Accession number :
- edsair.doi.dedup.....5dbf868f5b6c75019206cd2b1bead8b8