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

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.

Killer cell immunoglobulin-like receptor 2DL4 is expressed in and suppresses the cell growth of Langerhans cell histiocytosis

“…Thus, the anti-KIR2DL4 agonistic antibody suppressed the growth of LCH cell line ELD-1. This antibody may be a useful therapeutic tool for LCH, as well as other antibodies targeting inhibitory receptors [ 10 , 19 – 21 ].…”

Semaphorins and Their Receptors in Hematological Malignancies

“…In both studies, however, it remained undetermined the identity of pro-survival factors produced by stromal cells in response to SEMA4D/Plexin-B1 signaling. Another study assessed the growth-suppressing activity of CD72, the low affinity receptor of SEMA4D, in acute myelogenous leukemia (AML) cells (11). In fact, CD72 ligation by an agonistic antibody, or by its natural ligand SEMA4D/CD100, suppressed the proliferation of the AML Kasumi-1 cells and induced apoptotic cell death.…”

“…In fact, CD72 ligation by an agonistic antibody, or by its natural ligand SEMA4D/CD100, suppressed the proliferation of the AML Kasumi-1 cells and induced apoptotic cell death. The implicated molecular mechanism depends on CD72 phosphorylation and SHP-1 recruitment, leading to de-phosphorylation of Src family kinases and JNK (11). Thus, multiple data support a pro-tumorigenic role of SEMA4D in leukemias, consistent with the current knowledge about this semaphorin in solid tumors (12).…”

The Role of Semaphorin 4D in Bone Remodeling and Cancer Metastasis

“…CD72 (also known as Lyb-2) is a 45-kDa type II transmembrane protein of the C-type lectin family ( 13 ) which is expressed throughout B-cell differentiation ( 14 ). The CD72 cytoplasmic domain contains two immune-receptor tyrosine-based inhibition motifs that recruit the tyrosine phosphatase SHP-1, resulting in inhibition of src family kinases and JNK and B cell inhibition ( 15 ). Sema4D engagement of CD72 triggers tyrosine dephosphorylation of CD72, leading to SHP-1 dissociation ( 10 ), thereby relieving CD72-mediated B cell inhibition.…”

“…While blocking the Sema4D/Plexin-B1 complex is of potential benefit in cancers and neuroinflammatory diseases, some cancers are growth inhibited by Sema4D signaling. In an acute myeloid leukemia cell line Kasumi-1, Sema4D binding of CD72, its preferred receptor in immune cells, leads to inhibition of growth and cell death, as a result of phosphorylation of CD72, the formation of the CD72–SHP-1 complex and dephosphorylation of src family kinases and JNK ( 15 ). Future development of Sema4D targeting should take into account the cellular context where Sema4D exerts its function.…”