• Molecules and Cells
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• v.38 no.6
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• pp.482-495
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• 2015

Sphingolipids such as ceramide, sphingosine-1-phosphate and sphingomyelin have been emerging as bioactive lipids since ceramide was reported to play a role in human leukemia HL-60 cell differentiation and death. Recently, it is well-known that ceramide acts as an inducer of cell death, that sphingomyelin works as a regulator for microdomain function of the cell membrane, and that sphingosine-1-phosphate plays a role in cell survival/proliferation. The lipids are metabolized by the specific enzymes, and each metabolite could be again returned to the original form by the reverse action of the different enzyme or after a long journey of many metabolizing/synthesizing pathways. In addition, the metabolites may serve as reciprocal biomodulators like the rheostat between ceramide and sphingosine-1-phosphate. Therefore, the change of lipid amount in the cells, the subcellular localization and the downstream signal in a specific subcellular organelle should be clarified to understand the pathobiological significance of sphingolipids when extracellular stimulation induces a diverse of cell functions such as cell death, proliferation and migration. In this review, we focus on how sphingolipids and their metabolizing enzymes cooperatively exert their function in proliferation, migration, autophagy and death of hematopoetic cells, and discuss the way developing a novel therapeutic device through the regulation of sphingolipids for effectively inhibiting cell proliferation and inducing cell death in hematological malignancies such as leukemia, malignant lymphoma and multiple myeloma.

• Preventive Nutrition and Food Science
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• v.9 no.3
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• pp.265-269
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• 2004

Prunus mandshurica var. glabra Nakai (Rosaceae) is widely distributed in South Korea and bears a fruit with a bitter and astringent taste. An ethyl acetate-soluble extract of Prunus mandshurica was found to exhibit significant cytotoxicity against human leukemia cell lines. Bioassay-directed fractionation of this extract using an MTT(3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) cell proliferation assay as a monitor led to the isolation of the bioactive compounds. Two compounds, 1 and 2 were subsequently found to mediate cytotoxicity against U937, human monocytic leukemia cells. The 50% growth inhibitory concentrations ($IC_{50}$/) of compounds 1 and 2 on U937 were 40 and 62 $\mu\textrm{g}$/mL, respectively.

• Journal of Oral Medicine and Pain
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• v.42 no.2
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• pp.49-52
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• 2017

Leukemia is a malignant disease characterized by uncontrolled clonal proliferation of white blood cells. It is classified depending on clinical course of disease (acute or chronic) and the primary hematopoietic cell line affected (myeloid or lymphoid). Leukemia is often associated with orofacial manifestations, such as oral bleeding, petechiae, oral ulceration, gingival enlargement, mucosal pallor and mental nerve neuropathy. However, trismus has been rarely reported as a sign of leukemia. We present a case of trismus caused by acute lymphoblastic leukemia and emphasize the importance of orofacial manifestations in the early diagnosis of leukemia.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3715-3721
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• 2015

Leukemia is a clonal disorder with blocked normal differentiation and cell death of hematopoietic progenitor cells. Traditional modalities with most used radiation and chemotherapy are nonspecific and toxic which cause adverse effects on normal cells. Differentiation inducing therapy forcing malignant cells to undergo terminal differentiation has been proven to be a promising strategy. However, there is still scarce of potent differentiation inducing agents. We show here that Angelica sinensis polysaccharide (ASP), a major active component in Dong quai (Chinese Angelica sinensis), has potential differentiation inducing activity in human chronic erythro-megakaryoblastic leukemia K562 cells. MTT assays and flow cytometric analysis demonstrated that ASP inhibited K562 cell proliferation and arrested the cell cycle at the G0/G1 phase. ASP also triggered K562 cells to undergo erythroid differentiaton as revealed by morphological changes, intensive benzidine staining and hemoglobin colorimetric reaction, as well as increased expression of glycophorin A (GPA) protein. ASP induced redistribution of STAT5 protein from the cytoplasm to the nucleus. Western blotting analysis further identified that ASP markedly sensitized K562 cells to exogenous erythropoietin (EPO) by activating EPO-induced JAK2/STAT5 tyrosine phosphorylation, thus augmenting the EPO-mediated JAK2/STAT5 signaling pathway. On the basis of these findings, we propose that ASP might be developed as a potential candidate for chronic myelogenous leukemia inducing differentiation treatment.

• The Korean Journal of Cytopathology
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• v.19 no.2
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• pp.168-172
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• 2008

T-cell prolymphocytic leukemia (T-PLL) is a rare, mature T-cell lymphoproliferative disorder with a post-thymic mature T-cell phenotype. The disease is characterized by rapidly rising lymphocytosis, lym-phadenopathy, and splenomegaly. The clinical course is usually aggressive and progresses with frequent skin lesions and serous effusions. In 25% of cases, leukemic cells are small and tumor cells may not have a discrete nucleolus under light microscopy. Although the presence of characteristic cytoplasmic protrusions or blebs in tumor cells is a common morphologic finding in the peripheral blood film irrespective of the nuclear features, small cell variants lacking the typical nuclear features can cause diagnostic problems in clinical cytology. Furthermore, the small leukemic cells can share some cytologic findings with lymphocyte-rich serous effusions caused by non-neoplastic reactive lymphocytosis as well as other small lymphocytic lymphoproliferative disorders. Here, we describe the cytological findings of ascitic fluid complicated by small cell variant T-PLL in a 54-year-old man, the cytology of which was initially interpreted as small lymphocytic malignancy such as small lymphocytic lymphoma/chronic lymphocytic leukemia.

• BLOOD RESEARCH
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• v.53 no.4
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• pp.325-329
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• 2018

• The Journal of the Korea Contents Association
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• v.12 no.2
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• pp.339-348
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• 2012

Acute promyelocytic leukemia (APL) is a cancer of the blood and bone marrow. Although all-trans retionic acid (ATRA) is the agents for ALP therapy, there are various side effects. For overcome this problem, we need the development of new therapeutic agents for APL. A number of bacteria produce various virulence factors with cytotoxic effects on human cancer cells. To understand the anti-cancer effect of Listeria monocytogenes on APL, we examined alteration of the cell viability, apoptosis and cell cycle arrest of the human promyelocytic leukemia cell line, HL-60 cells. The cell supernatant (LmSup) and the extract of L. monocytogenes (LmE) inhibited the cell viability and induced apoptosis of HL-60 cells. These cytotoxic effect of LmSup and LmE mediated by modulation of cell cycle and ROS production. These results indicate that released or included bacterial molecules from L. monocytogenes have a cytotoxicity in HL-60 cells. Therefore, LmSup and LmE may be used as the potential target for the treatment of cancer induced by HL-60 cells.

• Imaging Science in Dentistry
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• v.46 no.4
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• pp.273-278
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• 2016

Plasma cell leukemia (PCL) is an aggressive form of multiple myeloma where there is hematogenous spread of abnormal plasma cells into the periphery. This is opposed to multiple myeloma, where the abnormal plasma cells stay in the bone marrow. PCL is more common in males than females, and is also more common in African-Americans than Caucasians. Signs and symptoms of PCL include, but are not limited to, renal insufficiency, hypercalcemia, anemia, lytic bone lesions, thrombocytopenia, hepatomegaly, and splenomegaly. Here, we discussed a case of a 71-year-old Caucasian female recently diagnosed with primary PCL with radiographic features of this disease throughout the body, with an emphasis on the maxillofacial skeleton and relevance from a dental standpoint.

• IMMUNE NETWORK
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• v.9 no.2
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• pp.35-40
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• 2009

Although Rap GTPases of the Ras family remained enigmatic for years, extensive studies in this decade have revealed diverse functions of Rap signaling in the control of cell proliferation, differentiation, survival, adhesion, and movement. With the use of gene-engineered mice, we have uncovered essential roles of endogenous Rap signaling in normal lymphocyte development of both T- and B-lineage cells. Deregulation of Rap signaling, on the other hand, results in the development of characteristic leukemia in manners highly dependent on the contexts of cell lineages. These results highlight crucial roles of Rap signaling in the physiology and pathology of lymphocyte development.

• Archives of Pharmacal Research
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• v.19 no.2
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• pp.91-94
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• 1996

In the course of a search for antitumor agents, we found that the extract of Curcuma longa was effective in inducing apoptosis or programmed cell death (PCD) in human myeloid leukemia cells (HL-60). Active compounds for PCD were isolated from the hexanic extraction of the rhizome of Curcuma longa. With the several chromatographies, and spectral data, they were identified as ar-turmerone and $\beta-atlantone$. The present results demonstrate that the exposure of human myeloid leukemia HL-60 cells to clinically achievable concentrations of arturmerone (TU) or .$\beta-atlantone$(AT) produced internucleosomal DNA fragmentation of approximately 200 base-pair multiples, and the morphological changes characteristic of cells undergoing apoptosis or PCD. This findings suggest that these agents may exert their antitumoral activity, in part, through induction of apoptosis(PCD).