• Annals of Laboratory Medicine
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• v.38 no.6
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• pp.495-502
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• 2018

Background: Molecular genetic abnormalities are observed in over 90% of chronic myelomonocytic leukemia (CMML) cases. Recently, several studies have demonstrated the negative prognostic impact of ASXL1 mutations in CMML patients. We evaluated the prognostic impact of ASXL1 mutations and compared five CMML prognostic models in Korean patients with CMML. Methods: We analyzed data from 36 of 57 patients diagnosed as having CMML from January 2000 to March 2016. ASXL1 mutation analysis was performed by direct sequencing, and the clinical and laboratory features of patients were compared according to ASXL1 mutation status. Results: ASXL1 mutations were detected in 18 patients (50%). There were no significant differences between the clinical and laboratory characteristics of ASXL1-mutated ($ASXL1^+$) CMML and ASXL1-nonmutated ($ASXL1^-$) CMML patients (all P >0.05). During the median follow-up of 14 months (range, 0-111 months), the overall survival (OS) of $ASXL1^+$ CMML patients was significantly inferior to that of $ASXL1^-$ CMML patients with a median survival of 11 months and 19 months, respectively (log-rank P =0.049). An evaluation of OS according to the prognostic models demonstrated inferior survival in patients with a higher risk category according to the Mayo molecular model (log-rank P =0.001); the other scoring systems did not demonstrate a significant association with survival. Conclusions: We demonstrated that ASXL1 mutations, occurring in half of the Korean CMML patients examined, were associated with inferior survival. ASXL1 mutation status needs to be determined for risk stratification in CMML.

• The Journal of Korean Medicine
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• v.29 no.3
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• pp.88-99
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• 2008

Objectives: In order to identify the anti-inflammatory and analgesic properties of Salvia miltiorrhiza (Dan-Sam), widely used in Korean traditional medicine, an in vitro screening system was designed using pGL3, a luciferase reporter vector, and the tumor necrosis factor (TNF)-${\alpha}$ and cyclooxygenase (COX)-2 as target genes. Methods: The promoter regions of each gene were generated by PCR using the human chromosome as template DNA, and inserted into pGL3 vector with Kpn I and Hind III. The final construct was transfected into human myelomonocytic leukemia cells (U-937) that could be differentiated and activated by phorbol 12-myristate 13-acetate (PMA) or lipopolysaccharide (LPS). Using this system, the anti-inflammatory and analgesic effects of several herbal extracts regarded to have the medicinal effects of diminishing body heat and complementing Qi were tested. The chemicals PD98059 and berberine chloride were used as controls of the transcriptional inhibitors of TNF-${\alpha}$ and COX-2, respectively. Results: Salvia miltiorrhiza (Dan-Sam) demonstrated significant decrease of TNF-${\alpha}$ and COX-2 mRNA in the in vitro assay system. In MTT assay, Salvia miltiorrhiza (Dan-Sam) did not significantly inhibit the survival and proliferation of human myelomonocytic leukemia cells (U-937). Conclusions: Salvia miltiorrhiza (Dan-Sam) was found to exhibit the significant medicinal properties of anti-inflammatory and analgesic effects.

• Journal of Periodontal and Implant Science
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• v.44 no.6
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• pp.293-299
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• 2014

Purpose: Systemic disease can manifest oral signs at an early phase, which may be crucial for the diagnosis and timing of treatment. This report describes two patients who presented with gingival enlargement as an early sign of acute leukemia. Methods: Two patients presented with oral symptoms including severe gingival enlargement. The progress of their symptoms was associated with underlying systemic disease. Results: The patients were transferred to the Department of Hematology and diagnosed with acute myelomonocytic leukemia. They received appropriate treatment and survived. Conclusions: Gingival enlargement can be caused by underlying systemic diseases. Accurate diagnosis and timely referral are important for preventing a fatal situation. It must be emphasized that some oral signs and symptoms may be closely correlated with systemic diseases.

• Clinical and Experimental Pediatrics
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• v.48 no.2
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• pp.178-185
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• 2005

Purpose : The purpose of this study was to evaluate the outcome of children with juvenile myelomonocytic leukemia(JMML) treated with allogeneic hematopoietic stem cell transplantation(allo-HSCT). Methods : Eleven JMML patients aged 8-39 months underwent allo-HSCT. The sources of grafts were unrelated donors(n=7), HLA-matched siblings(n=3) and an HLA 1-antigen mismatched familial donor. All patients had received chemotherapy ${\pm}13$-cis-retinoic acid(CRA) before transplant, and CRA was used, posttransplant, in six patients. Results : Only three patients were in complete remission(CR) at the time of transplantation. Initial chimeric status revealed complete donor chimerism(CC) in five patients, mixed chimerism(MC) in five and autologous recovery(AR) in one. One patient with MC having persistent splenomegaly eventually turned to CC and CR after rapid tapering of cyclosporine, combined with daily use of CRA. An AR case relapsed shortly after transplant but was rescued with second, unrelated cord blood transplantation. Ultimately, six patients are alive, event-free, with a median follow-up of 15.5 months posttransplant. All three deaths occurred in patients who failed to achieve CC, leading to disease progression. Conclusion : We suggest that graft-versus-leukemia effect play an important role and CRA a possible role in posttransplant leukemic involution in JMML. In patients whose leukemic burden is still high with MC after transplant, early tapering of immunosuppressants and introduction of CRA might provide a chance of a cure for some patients.

• Journal of Oral Medicine and Pain
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• v.30 no.3
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• pp.329-336
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• 2005

We examined the effect of PQQ, as a scavenger of superoxide, on osteoclast-like cell formation and on mature osteoclast function. To determine whether PQQ scavenges the superoxide, nitroblue tetrazolium (NBT) staining, which is a method to detect superoxide, was performed on HD-11 cells which are a chick myelomonocytic cell line having tartrate-resistant acid phosphatase (TRAP) activity in response to 1,25-dihydroxyvitamin $D_3\;[1,25(OH)_2D_3]$. Histochemical study of TRAP was also performed on HD-11 cells. PQQ inhibited the TRAP-positive multinucleated cell formation of chicken bone marrow cells was also examined. The addition of 20 ${\mu}M$ PQQ inhibited the formation of TRAP-positive multinucleated cell. When chicken osteoclasts were cultured on dentin slices, treatment of 20 ${\mu}M$ PQQ resulted in a significant decrease in dentin resorption by osteoclasts in terms of total resorption area and number of resorption pits. The present data suggest that PQQ, possibly as a scavenger of superoxide ion, inhibits the osteoclastic differentiation and bone resorption.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2187-2191
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• 2015

Background: Protrusive structures formed by migrating and invading cells are termed lamellipodia, filopodia, invadopodia and podosomes. Lamellipodia and filopodia appear on the leading edges of migrating cells and function to command the direction of the migrating cells. Invadopodia and podosomes are special F-actin-rich matrix-degrading structures that arise on the ventral surface of the cell membrane. Invadopodia are found in a variety of carcinomatous cells including squamous cell carcinoma of head and neck region whereas podosomes are found in normal highly motile cells of mesenchymal and myelomonocytic lineage. Invadopodia-associated protein markers consisted of 129 proteins belonging to different functional classes including WASP, NWASP, cortactin, Src kinase, Arp 2/3 complex, MT1-MMP and F-actin. To date, our current understanding on the role(s) of these regulators of actin dynamics in tumors of the orofacial region indicates that upregulation of these proteins promotes invasion and metastasis in oral squamous cell carcinoma, is associated with poor/worst prognostic outcome in laryngeal cancers, contributes to the persistent growth and metastasis characteristics of salivary gland adenoid cystic carcinoma, is a significant predictor of increased cancer risk in oral mucosal premalignant lesions and enhances local invasiveness in jawbone ameloblastomas.

• Molecules and Cells
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• v.43 no.2
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• pp.145-152
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• 2020

RUNX1 plays an important role in the regulation of normal hematopoiesis. RUNX1 mutations are frequently found and have been intensively studied in hematological malignancies. Germline mutations in RUNX1 cause familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML). Somatic mutations of RUNX1 are observed in various types of hematological malignancies, such as AML, acute lymphoblastic leukemia (ALL), myelodysplastic syndromes (MDS), myeloproliferative neoplasm (MPN), chronic myelomonocytic leukemia (CMML), and congenital bone marrow failure (CBMF). Here, we systematically review the clinical and molecular characteristics of RUNX1 mutations, the mechanisms of pathogenesis caused by RUNX1 mutations, and potential therapeutic strategies to target RUNX1-mutated cases of hematological malignancies.

• Molecules and Cells
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• v.43 no.2
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• pp.153-159
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• 2020

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder. NF1 patients are predisposed to formation of several type solid tumors as well as to juvenile myelomonocytic leukemia. Loss of NF1 results in dysregulation of MAPK, PI3K and other signaling cascades, to promote cell proliferation and to inhibit cell apoptosis. The RUNX1 gene is associated with stem cell function in many tissues, and plays a key role in the fate of stem cells. Aberrant RUNX1 expression leads to context-dependent tumor development, in which RUNX1 may serve as a tumor suppressor or an oncogene in specific tissue contexts. The co-occurrence of mutation of NF1 and RUNX1 is detected rarely in several cancers and signaling downstream of RAS-MAPK can alter RUNX1 function. Whether aberrant RUNX1 expression contributes to NF1-related tumorigenesis is not fully understood. This review focuses on the role of RUNX1 in NF1-related tumors and blood disorders, and in sporadic cancers.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.3
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• pp.369-376
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• 1998

This report shows that hydroxyl radical, generated by a Fenton reaction involving adenosine $5'-diphosphate/Fe^{2+}$ complex ($5-15\;{\mu}M$) and $H_2O_2$ ($2\;{\mu}M$), induced differentiation of HL-60 cells in a dose- and time-dependent manner. This is evidenced by the increases in 12-O-tetradecanoylphorbol 13-acetate- and fMLP-stimulated superoxide production capability. The cells exposed to hydroxyl radical for defined periods (24∼96 hr) continued to differentiate even after the hydroxyl radical generating system had been removed. The differentiated cells displayed fMLP-stimulated calcium mobilization and increased expression of myeloid-specific antigen CD11b and CD14. The extent of the differentiation was markedly reduced by desferrioxamine ($100\;{\mu}M$), dimethylthiourea (5 mM), N,N'-diphenyl-1,4-phenylenediamine ($2\;{\mu}M$), and N-acetyl-L-cysteine (5 mM). The induction of differentiation by hydroxyl radical was enhanced by 3-isobutyl-1-methylxanthine ($200\;{\mu}M$) and Ro-20-1724 ($8\;{\mu}M$), and inhibited by dipyridamole (2 ${\mu}M$). These results suggest that hydroxyl radicals may induce commitment of HL-60 cells to differentiate into more mature cells of myelomonocytic lineage through specific signal-transduction pathway that is modulated by phosphodiesterase inhibitors.

• Parasites, Hosts and Diseases
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• v.46 no.3
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• pp.145-151
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• 2008

During Toxoplasma gondii infection, macrophages, dendritic cells, and neutrophils are important sources of pro-inflammatory cytokines from the host. To counteract the pro-inflammatory activities, T. gondii is known to have several mechanisms inducing down-regulation of the host immunity. In the present study, we analyzed the production of pro- and anti-inflammatory cytokines from a human myelomonocytic cell line, THP-1 cells, in response to treatment with T. gondii lysate or lipopolysaccharide (LPS). Treatment of THP-1 cells with LPS induced production of IL-12, TNF-$\alpha$, IL-8, and IL-10. Co-treatment of THP-1 cells with T. gondii lysate inhibited the LPS-induced IL-12, IL-8 and TNF-$\alpha$ expression, but increased the level of IL-10 synergistically. IL-12 and IL-10 production was down-regulated by anti-human toll-like receptor (TLR)-2 and TLR4 antibodies. T. gondii lysate triggered nuclear factor (NF)-${\kappa}B$-dependent IL-8 expression in HEK293 cells transfected with TLR2. It is suggested that immunosuppression induced by T. gondii lysate treatment might occur via TLR2-mediated NF-${\kappa}B$ activation.