Ligation of the CD44 adhesion molecule reverses blockage of differentiation in human acute myeloid leukemia.
Blockage in myeloid differentiation characterizes acute myeloid leukemia (AML); the stage of the blockage defines distinct AML subtypes (AML1/2 to AML5). Differentiation therapy in AML has recently raised interest because the survival of AML3 patients has been greatly improved using the differentiating agent retinoic acid. However, this molecule is ineffective in other AML subtypes. The CD44 surface antigen, on leukemic blasts from most AML patients, is involved in myeloid differentiation. Here, we report that ligation of CD44 with specific anti-CD44 monoclonal antibodies or with hyaluronan, its natural ligand, can reverse myeloid differentiation blockage in AML1/2 to AML5 subtypes. The differentiation of AML blasts was evidenced by the ability to produce oxidative bursts, the expression of lineage antigens and cytological modifications, all specific to normal differentiated myeloid cells. These results indicate new possibilities for the development of CD44-targeted differentiation therapy in the AML1/2 to AML5 subtypes.
Charrad
R S
RS
Inserm U268, Laboratoire de différenciation hématopoiétique normale et leucémique, Hôpital Paul-Brousse, Villejuif, France.
Li
Y
Y
Delpech
B
B
Balitrand
N
N
Clay
D
D
Jasmin
C
C
Chomienne
C
C
Smadja-Joffe
F
F
D000208:Acute Disease; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000494:pharmacology; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D016179:Granulocyte Colony-Stimulating Factor / Q000187:drug effects / Q000235:genetics; D006098:Granulocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D018960:Hyaluronan Receptors / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D016256:Lewis X Antigen / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000187:drug effects / Q000235:genetics; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000187:drug effects / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D016897:Respiratory Burst; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D018960:Hyaluronan Receptors; D016256:Lewis X Antigen; D018950:Lipopolysaccharide Receptors; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; D016179:Granulocyte Colony-Stimulating Factor; D014212:Tretinoin; D016173:Macrophage Colony-Stimulating Factor; D006820:Hyaluronic Acid