記述言語：英語   掲載種別：研究論文（学術雑誌）  

The signaling lymphocytic activation molecule family 3 (SLAMF3) is a member of the immunoglobulin superfamily expressed on T, B, and natural killer cells and modulates the activation and cytotoxicity of these cells. SLAMF3 is also expressed on plasma cells from patients with multiple myeloma (MM), although its role in MM pathogenesis remains unclear. This study found that SLAMF3 is highly and constitutively expressed on MM cells regardless of disease stage and that SLAMF3 knockdown/knockout suppresses proliferative potential and increases drug-induced apoptosis with decreased levels of phosphorylated ERK protein in MM cells. SLAMF3-overexpressing MM cells promote aggressive myeloma behavior in comparison with cytoplasmic domain-truncated SLAMF3 (ΔSLAMF3) cells. SLAMF3 interacts directly with adaptor proteins SH2 domain-containing phosphatase 2 (SHP2) and growth factor receptor bound 2 (GRB2), which also interact with each other. SLAMF3 knockdown, knockout, ΔSLAMF3, and SHP2 inhibitor-treated MM cells decreased phosphorylated ERK protein levels. Finally, serum soluble SLAMF3 (sSLAMF3) levels were markedly increased in advanced MM. Patients with high levels of sSLAMF3 progressed to the advanced stage significantly more often and had shorter progression-free survival times than those with low levels. This study revealed that SLAMF3 molecules consistently expressed on MM cells transmit MAPK/ERK signals mediated via the complex of SHP2 and GRB2 by self-ligand interaction between MM cells and induce a high malignant potential in MM. Furthermore, high levels of serum sSLAMF3 may reflect MM disease progression and be a useful prognostic factor. IMPLICATIONS: SLAMF3 may be a new therapeutic target for immunotherapy and novel agents such as small-molecule inhibitors.

DOI： 10.1158/1541-7786.MCR-19-0391

PubMed

researchmap

記述言語：英語   出版者・発行元：日本骨髄腫学会  

researchmap

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

A 51-year-old man was diagnosed with stage IV mantle cell lymphoma based on terminal ileum biopsy and treated with the R-CHOP regimen. Abdominal CT to assess continuous fever after three courses of R-CHOP revealed three low-density areas in the liver. PCR of the fluid obtained by percutaneous drainage revealed Entamoeba histolytica positivity, although the cultures were negative. Metronidazole treatment achieved cure. The patient was not a homosexual but had an 8-month stay in Lesotho 21 years ago, leading to the possibility that E. histolytica infection at the time continued as an asymptomatic colonization until the initiation of corticosteroid-containing chemotherapy.

DOI： 10.11406/rinketsu.60.929

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

The signaling lymphocytic activation molecule family (SLAMF7; also known as CS1 or CD319) is highly expressed on plasma cells from multiple myeloma (MM) as well as natural killer (NK) cells and is a well-known therapeutic target of elotuzumab. The objective of this study was to evaluate the clinical significance of serum soluble SLAMF7 (sSLAMF7) levels in patients with MM (n=103) and furthermore the impact of sSLMF7 on the antitumor activity of anti-SLAMF7 antibody. Thirty-one percent of MM patients, but not patients with monoclonal gammopathy of undetermined significance and healthy controls, had detectable levels of serum sSLAMF7, which were significantly increased in advanced MM patients. Further, MM in sSLAMF7-postive patients exhibited aggressive clinical characteristics with shorter progression-free survival times in comparison with sSLAMF7-negative patients. In responders to MM therapy, the levels of sSLAMF7 were undetectable or decreased compared with those before treatment. In addition, the anti-SLAMF7 antibody-mediated antibody-dependent cellular cytotoxicity of NK cells against MM cell lines was inhibited by recombinant SLAMF7 protein. Thus, our findings suggest that high concentrations of sSLAMF7, which could transiently suppress the therapeutic effects of elotuzumab, may be a useful indicator of disease progression in MM patients.

DOI： 10.18632/oncotarget.26196

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

T-cell immunoglobulin mucin-3 (Tim-3), an inhibitory immune checkpoint receptor, is highly expressed on acute myeloid leukemia cells and its ligand galectin-9 is reported to drive leukemic progression by binding with Tim-3. However, it remains unclear whether the Tim-3-galectin-9 pathway is associated with the pathophysiology of myelodysplastic syndromes (MDS). Thus, we investigated the expression and function of Tim-3 and the clinical impact of its ligand galectin-9 in MDS. Tim-3 expression levels on MDS blasts by CD45/side-scatter or CD34/CD45 gating were increased as MDS progressed to the advanced stage. Tim-3 expression in the MDS blasts was upregulated in the presence of the cell culture supernatant of human stromal cells or the MDS-related cytokine transforming growth factor-β1. The proliferation of Tim-3+ MDS blasts was inhibited by the blockade of anti-Tim-3 antibody. Furthermore, plasma levels of galectin-9 were elevated as MDS progressed to the advanced stage in 70 MDS/acute leukemia transformed from MDS patients and was a prognostic factor in 40 MDS patients. Our data demonstrated that the Tim-3-galectin-9 pathway is associated with the pathogenesis and disease progression of MDS. These findings provide new insight into potential immunotherapy targeting the galectin-9-Tim-3 pathway in MDS.

DOI： 10.18632/oncotarget.21492

PubMed

researchmap

記述言語：英語   出版者・発行元：AMER SOC HEMATOLOGY  

Web of Science

researchmap

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

The NCCN-International Prognostic Index (IPI) is reported to be more powerful than the former IPI for predicting survival in the rituximab era. To evaluate the NCCN-IPI in our institutions, we analyzed 188 patients with diffuse large B-cell lymphoma treated with rituximab plus CHOP or THP-COP chemotherapy. The 5-year overall survival rates of patients with low, low-intermediate, high-intermediate, and high risk were 90%, 76%, 64%, and 34%, respectively. Although there was no difference in overall survival between patients 61-75 and those >75 years of age, the NCCN-IPI is useful for classifying prognostically relevant subgroups of Japanese patients.

DOI： 10.11406/rinketsu.56.915

Scopus

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

A 72-year-old woman with a history of diffuse large B cell lymphoma and recent recurrence visited our department complaining of several painful edematous nodules with blisters on her face. She had iteratively developed cutaneous eruptions after every treatment with granulocyte colony-stimulating factor (G-CSF) for neutropenia, and each time the eruption improved after the cessation of the G-CSF treatment. The blisters became crusty and the skin lesions slightly improved, but on the 24th hospital day, the eruption formed painful erythematous nodules with erosion, and the patient also developed a high fever of up to 38°C. A biopsy specimen showed a dermal infiltrate of increased and enlarged plump histiocytes, some of which indicated karyomitosis with a small number of lymphocytes. No increase in the number of eosinophils or neutrophils was noted. These eruptions lasted for 15 days and disappeared with the recovery of the peripheral blood count and attendant cessation of G-CSF. We diagnosed this case as G-CSF-induced granulomatous dermatitis with enlarged histiocytes. Several cases with maculopapular rash and dermal inflammatory infiltrate composed of interstitially arranged large histiocytes have been reported. However, to the best of our knowledge, this is the first case report of G-CSF-induced granulomatous dermatitis with enlarged histiocytes clinically manifesting as painful edematous nodules with a high fever, similar to Sweet's syndrome. We speculated that the infiltrating cells were not neutrophils but histiocytes, presumably because of agranulocytosis.

DOI： 10.1111/1346-8138.12772

PubMed

researchmap

記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：FERRATA STORTI FOUNDATION  

Web of Science

researchmap

記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：CIG MEDIA GROUP, LP  

DOI： 10.1016/j.clml.2017.03.069

Web of Science

researchmap

記述言語：日本語   出版者・発行元：日本骨髄腫学会  

J-GLOBAL

researchmap

記述言語：日本語   出版者・発行元：日本骨髄腫学会  

J-GLOBAL

researchmap

記述言語：英語   出版者・発行元：(一社)日本血液学会-東京事務局  

researchmap