title: [CXCR4: a new therapeutic target of the leukaemic cell? Role of the SDF-1/CXCR4 axis in acute myeloid leukaemia].
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.
authors: Institut de cancérologie Lucien-Neuwirth, Service d'hématologie, 108 bis, avenue Albert-Raimond, 42270 Saint-Priest-en-Jarez, France, Université Jean-Monnet, UMR 5239, Laboratoire de biologie moléculaire de la cellule, 42000 Saint-Etienne, France.
authors: Emmanuelle
authors: E
authors: Tavernier
authors: CHU Saint-Etienne, Hôpital Nord, laboratoire d'hématologie, 42270 Saint-Priest-en-Jarez, France.
authors: Carmen
authors: C
authors: Aanei
authors: Université Jean-Monnet, UMR 5239, Laboratoire de biologie moléculaire de la cellule, 42000 Saint-Etienne, France, CHU Saint-Etienne, Hôpital Nord, laboratoire d'hématologie, 42270 Saint-Priest-en-Jarez, France.
authors: Françoise
authors: F
authors: Solly
authors: Université Jean-Monnet, UMR 5239, Laboratoire de biologie moléculaire de la cellule, 42000 Saint-Etienne, France, CHU Saint-Etienne, Hôpital Nord, laboratoire d'hématologie, 42270 Saint-Priest-en-Jarez, France.
authors: Pascale
authors: P
authors: Flandrin-Gresta
authors: Université Jean-Monnet, UMR 5239, Laboratoire de biologie moléculaire de la cellule, 42000 Saint-Etienne, France, CHU Saint-Etienne, Hôpital Nord, laboratoire d'hématologie, 42270 Saint-Priest-en-Jarez, France.
authors: Lydia
authors: L
authors: Campos
authors: Institut de cancérologie Lucien-Neuwirth, Service d'hématologie, 108 bis, avenue Albert-Raimond, 42270 Saint-Priest-en-Jarez, France, Université Jean-Monnet, UMR 5239, Laboratoire de biologie moléculaire de la cellule, 42000 Saint-Etienne, France.
authors: Denis
authors: D
authors: Guyotat
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D054377:Chemokine CXCL12 / Q000502:physiology*; D002986:Clinical Trials as Topic; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D051379:Mice; D058990:Molecular Targeted Therapy / Q000379:methods*; D011379:Prognosis; D054387:Receptors, CXCR / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction; D059016:Tumor Microenvironment / Q000502:physiology
chemical_list: C501896:ACKR3 protein, human; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D054387:Receptors, CXCR; D019718:Receptors, CXCR4; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: CXCR4; SDF-1; acute myeloid leukaemia; prognostic factors; therapeutic target