CD72 regulates the growth of KIT-mutated leukemia cell line Kasumi-1.
Gain-of-function mutations in KIT, a member of the receptor type tyrosine kinases, are observed in certain neoplasms, including mast cell tumors (MCTs) and acute myelogenous leukemias (AMLs). A MCT line HMC1.2 harboring the KIT mutation was reported to express CD72, which could suppress the cell proliferation. Here, we examined the ability of CD72 to modify the growth of AMLs harboring gain-of-function KIT mutations. CD72 was expressed on the surface of the AML cell line, Kasumi-1. CD72 ligation by an agonistic antibody BU40 or by a natural ligand CD100, suppressed the proliferation of the Kasumi-1 cells and enhanced cell death, as monitored by caspase-3 cleavage. These responses were associated with the phosphorylation of CD72, the formation of the CD72 - SHP-1 complex and dephosphorylation of src family kinases and JNK. Thus, these results seemed to suggest that CD72 was the therapeutic potential for AML, as is the case of MCTs.
Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan.
Tatsuki R
TR
Kataoka
1] Department of Immunopathology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan [2] WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan.
Atsushi
A
Kumanogoh
Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan.
Masahiro
M
Hirata
Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan.
Koki
K
Moriyoshi
Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan.
Chiyuki
C
Ueshima
Department of Hematology and Oncology, Kyoto University Hospital, Kyoto, Japan.
Masahiro
M
Kawahara
Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan.
Tatsuaki
T
Tsuruyama
Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan.
Hironori
H
Haga
D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D010766:Phosphorylation; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000235:genetics / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D039961:Semaphorins / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C093224:CD100 antigen; C064228:CD72 protein, human; D012333:RNA, Messenger; D039961:Semaphorins; D019009:Proto-Oncogene Proteins c-kit; D019061:src-Family Kinases; D048670:MAP Kinase Kinase 4; C509249:PTPN6 protein, human; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D053148:Caspase 3