HI44a, an anti-CD44 monoclonal antibody, induces differentiation and apoptosis of human acute myeloid leukemia cells.
CD44 is a cell surface antigen that expresses on leukemia blasts from most acute myeloid leukemia (AML) patients. It has been reported that ligation of CD44 with some specific anti-CD44 monoclonal antibodies can reverse the differentiation blockage of leukemia cell lines. In this study, the differentiation and apoptosis-inducing effects of HI44a, another anti-CD44 monoclonal antibody (IgG2a), were investigated on leukemia cells obtained from 31 patients with AML-M2, AML-M3, AML-M4 or AML-M5. When the AML cells were treated with HI44a, the percentage of nitroblue tetrazolium (NBT)+ cells was significantly increased. The expression of CD11b, CD14 and CD15 on treated AML cells was also increased compared to control AML cells. In addition, HI44a was found to induce apoptosis of leukemia cells, as evidenced by an annexin-V assay. The mean percentage of apoptotic cells in HI44a-treated AML cells was significantly increased compared to that in control AML cells. Moreover, the level of c-myc transcript expression on AML cells was found to be obviously decreased in all detected patients. These results indicate that HI44a effectively induces both differentiation and apoptosis of AML cells and suggest that this activity of the anti-CD44 antibody may be associated with its inhibitory effect on c-myc transcript expression.
State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
Guoli
G
Song
Xiaolong
X
Liao
Ling
L
Zhou
Lihua
L
Wu
Yi
Y
Feng
Zhong Chao
ZC
Han
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects*; D005260:Female; D016259:Genes, myc; D006801:Humans; D018960:Hyaluronan Receptors / Q000187:drug effects*; D007951:Leukemia, Myeloid / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016271:Proto-Oncogene Proteins c-myc / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; C522597:HI44a monoclonal antibody; D018960:Hyaluronan Receptors; D016271:Proto-Oncogene Proteins c-myc