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[CXCR4: a new therapeutic target of the leukaemic cell? Role of the SDF-1/CXCR4 axis in acute myeloid leukaemia]
- Source :
- Bulletin du cancer. 101(6)
- Publication Year :
- 2014
-
Abstract
- CXCR4, receptor of the chemokine SDF-1 (stromal cell-derived factor 1) plays a major role in the normal hematopoiesis but also in the biology of the leukaemic cell. This receptor is expressed on the surface of blasts and is a key molecule in "the anchoring" of the leukaemic stem cell (LSC) within the bone marrow niche. The interactions of the LSC with the bone marrow microenvironment promote survival signals and drug resistance. Recent flow cytometry analyses reported that CXCR4 expression levels have a major prognostic impact in acute myeloid leukaemia (AML). CXCR4 expression is associated with poor prognosis and can be useful to stratify patients, according to their phenotype, in order to establish risk-adapted strategies. Newly diagnosed AML are now routinely stratified according to molecular markers which guide prognosis and treatment. Many leukaemia are composed of multiples subclones with differential susceptibility to treatment and specific targeted therapies are missing. Despite therapeutic improvements for the treatment of AML, long term survival remains poor. Targeting CXCR4 is a novel promising approach of therapy. CXCR4 antagonists are used in combination with chemotherapy in preclinical and clinical studies. This review summarises our current knowledge regarding the key role of CXCR4 in AML and discusses how targeting this pathway could provide an interesting approach to eradicate the LSC.
- Subjects :
- Receptors, CXCR
Clinical Trials as Topic
Receptors, CXCR4
Granulocyte-Macrophage Colony-Stimulating Factor
Hematopoietic Stem Cells
Prognosis
Chemokine CXCL12
Hematopoietic Stem Cell Mobilization
Leukemia, Myeloid, Acute
Mice
Cell Movement
Granulocyte Colony-Stimulating Factor
Tumor Microenvironment
Animals
Humans
Molecular Targeted Therapy
Cell Proliferation
Signal Transduction
Subjects
Details
- Language :
- French
- ISSN :
- 17696917
- Volume :
- 101
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Bulletin du cancer
- Accession number :
- edsair.pmid..........77ad4f7a4155ef40df606132f6373a95