CD72 regulates the growth of KIT-mutated leukemia cell line Kasumi-1

Tatsuki R Kataoka; Atsushi Kumanogoh; Masahiro Hirata; Koki Moriyoshi; Chiyuki Ueshima; Masahiro Kawahara; Tatsuaki Tsuruyama; Hironori Haga

doi:10.1038/srep02861

CD72 regulates the growth of KIT-mutated leukemia cell line Kasumi-1

Sci Rep. 2013 Oct 4:3:2861. doi: 10.1038/srep02861.

Authors

Tatsuki R Kataoka¹, Atsushi Kumanogoh², Masahiro Hirata¹, Koki Moriyoshi¹, Chiyuki Ueshima¹, Masahiro Kawahara³, Tatsuaki Tsuruyama¹, Hironori Haga¹

Affiliations

¹ Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan.
² 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.
³ Department of Hematology and Oncology, Kyoto University Hospital, Kyoto, Japan.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antigens, CD / genetics
Antigens, CD / metabolism*
Antigens, Differentiation, B-Lymphocyte / genetics
Antigens, Differentiation, B-Lymphocyte / metabolism*
Blotting, Western
Caspase 3 / metabolism
Cell Proliferation*
Flow Cytometry
Gene Expression Regulation, Neoplastic*
Humans
Immunoenzyme Techniques
Immunoprecipitation
Leukemia, Myeloid, Acute / genetics
Leukemia, Myeloid, Acute / metabolism
Leukemia, Myeloid, Acute / pathology*
MAP Kinase Kinase 4 / genetics
MAP Kinase Kinase 4 / metabolism
Mutation / genetics*
Phosphorylation
Protein Tyrosine Phosphatase, Non-Receptor Type 6 / genetics
Protein Tyrosine Phosphatase, Non-Receptor Type 6 / metabolism
Proto-Oncogene Proteins c-kit / genetics*
RNA, Messenger / genetics
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Semaphorins / genetics
Semaphorins / metabolism
Tumor Cells, Cultured
src-Family Kinases / genetics
src-Family Kinases / metabolism

Substances

Antigens, CD
Antigens, Differentiation, B-Lymphocyte
CD100 antigen
CD72 protein, human
RNA, Messenger
Semaphorins
Proto-Oncogene Proteins c-kit
src-Family Kinases
MAP Kinase Kinase 4
PTPN6 protein, human
Protein Tyrosine Phosphatase, Non-Receptor Type 6
Caspase 3