The occurrence and development of many tumors all relate with abnormal expression of the Notch receptor. The role of different Notch receptors may be different, even contrary in different tissues at different stages of tumor development, as well as in the same system tumors. Notch signaling pathway plays an important role in cell proliferation, differentiation, apoptosis and tumor angiogenesis, and is as a meeting point for many important cell signaling pathway. Angiogenesis is regulated by complex interactions of multiple activators and inhibitors. Vascular endothelial growth factor (VEGF) and Notch signaling pathway are involved in such process. Many studies have confirmed that Notch signaling pathway plays a key role in the embryonic development and tumour angiogenesis. Recent studies have also revealed that Notch signaling pathway has many potential drug targets. Based on study of Notch signaling pathway and its molecular mechanism of leukemia, to design drugs effecting these targets to block and activate Notch signaling pathway for therapy of leukemia and angiogenesis diseases has a broad application prospects. This review summarises the components of Notch signaling pathway and the role of Notch signaling pathway in occurrence of leukemia and angiogenesis.
Animals ; Humans ; Leukemia ; metabolism ; pathology ; Neovascularization, Pathologic ; metabolism ; pathology ; Receptors, Notch ; metabolism ; Signal Transduction

The study was purposed to investigate the expression of CD73 on bone marrow nucleated cells (BMMNC) in various leukemia subtypes and its relationship with cell differentiation of leukemia. Immunocytochemistry staining and Wright-Giemsa staining of BMMNC from 75 cases of leukemia, 11 cases of myelodysplastic syndrome (MDS), 13 cases of non-leukemic patients and 9 healthy adults were performed, and the CD73(+) ratio in BMMNC and its relationship with differentiation of leukemia cells were analyzed. The results showed that the ratios of CD73(+) in BMMNC of com-B ALL, pre-B ALL and PLL were significantly higher than those in B-CLL (p < 0.05). CD73(+) ratios in AML subtypes of M(1), M(2a), t (8; 21), t (15; 17), M(4) and M(5) were markedly higher than those in MDS respectively, but in M(6) and MDS were lower and had no statistical difference between them. CD73(+) ratios in T-ALL, B-CLL, M(6), MDS, non-leukemia patients and healthy adults were close to each other and all of them were lower than those in B-ALL and other AML subtypes. It is concluded that the expression of CD73 is associated with leukemia subtype, differentiation and development. The higher differentiation of leukemia cells, the lower of CD73 expression in myeloid and B lymphoid leukemia, but T-ALL does not meet this pattern.
5'-Nucleotidase ; metabolism ; Adolescent ; Adult ; Cell Differentiation ; Humans ; Leukemia ; metabolism ; pathology ; Leukemia, Lymphocytic, Chronic, B-Cell ; metabolism ; Leukemia, Myeloid, Acute ; metabolism ; Myelodysplastic Syndromes ; metabolism ; Young Adult

OBJECTIVETo investigate the expression of cell surface E-cadherin in leukemia cell and the correlation of cell membrane localization of beta-catenin with E-cadherin expression.

METHODSBone marrow samples from 46 patients with acute leukemia and 17 normal donors were analyzed. Cell surface expression of E-cadherin and membrane localization of beta-catenin were labeled by immunofluorescence and analyzed with a laser scanning confocal fluorescence microscope in 14 specimens.

RESULTSCell surface E-cadherin expression level was significantly lower in leukemia cells (with the median fluorescent intensity of 16.78) than in normal hematopoietic progenitors (26.03). Correlation analysis showed that cell membrane localization of beta-catenin was correlated with E-cadherin expression (r = 0.74, P = 0.002). After E-cadherin was induced to express in leukemic cell by 5-Aza-CdR, membranous expression of beta-catenin was elevated while the nuclear expression reduced, indicating that E-cadherin-mediated adhesions could recruit beta-catenin to cell membrane.

CONCLUSIONThe loss of E-cadherin in leukemia cells may result in beta-catenin translocating to the nuclear and transcriptional activation of its target genes.

Cadherins ; metabolism ; Case-Control Studies ; Cell Membrane ; metabolism ; Humans ; Leukemia ; metabolism ; pathology ; beta Catenin ; metabolism

This study was aimed to investigate the expression of beta-catenin in leukemic cell lines and its relationship with pathogenesis of leukemia, semi-quantitative RT-PCR and Western blot were performed to detect the expression of beta-catenin in a panel of 15 human hematopoietic cell lines (U937, KG1a, Jurkat, K562, Namalwa, HEL, HUT78, Raji, Daudi, CEM, LCL-H, HL-60, NB4, J6-1, Ramos). Immunocytochemistry was performed in some of these cell lines to detect the location of beta-catenin. The results showed that the beta-catenin gene was widely expressed in most leukemic cell lines in various degree, the high expression of beta-catenin was found is U937, KG1a, Jurkat, K562 and Namalwa cells, middle expression of beta-catenin was observed in HEL, HUT78, Raji, Daudi and CEM cells, lower expression of beta-catenin was observed in LCL-H, HL-60, NB4, J6-1 and Ramos cells. The expression level of beta-catenin protein was identical to the expression level of beta-catenin mRNA. The expression of beta-catenin could be found in nuclei of all cells mentioned above, but their levels were different between them. Abundant beta-catenin also could be observed in nuclei of some leukemic cells by immunocytochemistry. It is concluded that overexpression of beta-catenin in leukemia cells, as a key mediator of Wnt signaling transduction pathway, indicates that the Wnt signaling transduction pathway may be aberrantly activated in leukemia.
Humans ; Leukemia ; metabolism ; pathology ; RNA, Messenger ; metabolism ; Signal Transduction ; Tumor Cells, Cultured ; beta Catenin ; metabolism

The study was aimed to explore the expression of stromal cell derived factor-1alpha (SDF-1alpha) and its receptor CXCR4, and their relationship with the extramedullary infiltration in acute lymphoblastic, grannulocytic and monocytic leukemia. 66 cases of acute leukemia included 31 cases of acute lymphoblatic leukemia (ALL), 20 cases of acute grannulocytic leukemia (M(2)) and 15 cases of acute monocytic leukemia (M(4)+M(5)). There were 41 cases with extramedullary infiltration and 25 cases without-extramedullary infiltration. Enzyme-linked immunoabsorbent assay (ELISA) and flow cytometry were used to determine expression of SDF-1alpha and CXCR4 respectively on leukemia cells in peripheral blood and bone marrow of different groups. The results showed that average plasma level of SDF-1alpha in the ALL, M(4)+M(5), M(2) patients and the normal control were 1317.87 +/- 220.76, 1339.79 +/- 187.06, 1063.70 +/- 190.74, 1908.34 +/- 135.55 (pg/ml) respectively. The average levels in the ALL, M(4)+M(5) and M(2) patients groups were lower than those in normal control group. Both levels in ALL and M(4)+M(5) patient groups were higher than that in M(2) patient group. The average levels of SDF-1alpha in patient group with extramedullary infiltration and patient groups without-extramedullary infiltration were 1252.49 +/- 263.12, 1234.91 +/- 185.50 (pg/ml) respectively. The former seemed as if higher than the latter, but without statistical significance. The MFI of CXCR4 expression in ALL, M(4)+M(5), M(2) patient group were 78.47 +/- 33.96, 67.21 +/- 24.29, 41.66 +/- 17.18, respectively. CXCR4 expression in ALL and M(4)+M(5) patient groups were higher than that in M(2) patient group (P > 0.05). There was no significant difference between the ALL and M(4)+M(5) patient group (P > 0.05). The MFI of CXCR4 expression in patients with extramedullary infiltration and patients without extramedullary infiltration were 81.72 +/- 27.63, 36.94 +/- 11.86 respectively. The former was higher than the latter (P < 0.05). It is concluded that the higher expression of CXCR4 on acute lymphoblatic and monocytic leukemia cells may be one of the molecular mechanisms of extramedullary infiltration in both kinds of leukemia. The average plasma levels of SDF-1alpha decreased in leukemia patients and this decrease not related to the extramedullar infiltration, which may be due to the SDF-1alpha local expression in the organ infiltrated.
Acute Disease ; Adolescent ; Adult ; Chemokine CXCL12 ; Chemokines, CXC ; biosynthesis ; genetics ; Child ; Child, Preschool ; Female ; Humans ; Leukemia ; metabolism ; pathology ; Leukemia, Myeloid, Acute ; metabolism ; pathology ; Leukemic Infiltration ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; metabolism ; pathology ; Receptors, CXCR4 ; biosynthesis ; genetics ; Stromal Cells ; metabolism

The bone marrow microenvironment composed of bone marrow cell, their secreted cytokines and extra-cellular medium (ECM), plays an important role in the process of hematopoiesis, hematonosis, apoptosis of malignant blood cells. In this review, the mechanisms for the protection of the leukemiic cells from the drug-induced apoptosis by bone marrow stromal cells and the related progress were summarized.
Apoptosis ; Apoptosis Regulatory Proteins ; metabolism ; Bone Marrow Cells ; metabolism ; pathology ; Drug Resistance, Neoplasm ; Humans ; Leukemia ; metabolism ; pathology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Stromal Cells ; metabolism ; pathology

Adult ; Biopsy ; CD3 Complex ; metabolism ; DNA Nucleotidylexotransferase ; metabolism ; Female ; Humans ; Leukemia, Biphenotypic, Acute ; metabolism ; pathology ; Lymph Nodes ; metabolism ; pathology ; Neck ; PAX5 Transcription Factor ; metabolism ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; metabolism ; pathology

To explore CD34(+) antigen expression in new diagnosed acute myeloid leukemia (AML) and analyze the prognosis for CD34(+) AML patients, the expression of antigen CD34 in 238 AML patients was detected by indirect immunofluorescence assay. The results showed that CD34 in 92 out of the 238 patients (38.7%) were positive, there was relationship between the CD34(+) expression and FAB subtypes (M(0), M(1)), and no CD34(+) expression was observed in M(3) subtypes. The complete remission rate of CD34(+) AML patients was 32%, which was lower than that of CD34(-) AML (61%). The lymphoid-associated antigen (CD7) was significantly increased in CD34(+) AML patients, compared with CD34(-) patients (P < 0.05). It is concluded that CD34(+) AML patients show poor prognosis and lower CR rate. The detection of CD34 expression is of some value in predicting prognosis in AML.
Adolescent ; Adult ; Aged ; Antigens, CD34 ; biosynthesis ; Antigens, CD7 ; biosynthesis ; Female ; Fluorescent Antibody Technique, Indirect ; Humans ; Leukemia, Monocytic, Acute ; metabolism ; pathology ; Leukemia, Myeloid, Acute ; metabolism ; pathology ; Leukemia, Myelomonocytic, Acute ; metabolism ; pathology ; Male ; Middle Aged ; Prognosis

In order to investigate the role of tryptase in angiogenesis of acute leukemia (AL), the expressions of tryptase and vascular endothelial growth factor (VEGF) in leukemic cells from 61 patients with AL were examined by using immunocytochemical method, and the correlation between tryptase and VEGF was analyzed. The results showed that tryptase positive expression was found in 15 out of 51 patients with acute myeloid leukemia (AML) (M(1) 1/3, M(2) 7/15, M(3) 5/20, M(5) 2/8). Tryptase positive expression was 29.4% in AML. However, none of 10 patients with acute lymphocytic leukemia (ALL) showed tryptase expression. There were no correlations between the amounts of cells with tryptase expression and patient age, WBC count, numbers of blood or marrow myeloblasts and neutrophil POX. VEGF expression was revealed in 41 patients with AML (80.4%) and only 3 with ALL (30%). Significant correlation has been found between the expression of tryptase and that of VEGF in AML-M(2) (r = 0.65, P < 0.05). It is concluded that tryptase appears to be a myeloid-specific marker in AML and may be involved in the angiogenesis of AML-M(2).
Biomarkers, Tumor ; biosynthesis ; Humans ; Immunohistochemistry ; Leukemia, Monocytic, Acute ; metabolism ; pathology ; Leukemia, Myeloid, Acute ; metabolism ; pathology ; Leukemia, Promyelocytic, Acute ; metabolism ; pathology ; Neovascularization, Pathologic ; Tryptases ; biosynthesis ; Vascular Endothelial Growth Factor A ; biosynthesis

The objective of this study was to estimate a novel apoptosis-promoting molecule PDCD5 expression in the bone marrow cells from adult acute myeloid leukemia (AML) for investigation of its significance in the pathogenesis of AML. Flow cytometry assay was used for detection of PDCD5 expression in the different groups of cells from bone marrow of AML patients and normal controls by using 21 monoclonal antibodies with different fluorescent markers. The PDCD5 expressions in bone marrow cells from some AML patients and normal controls were also detected by Western blot. The results showed that the mean PDCD5 fluorescence intensity in bone marrow nucleated cells (MNC) from the bone marrow of 36 untreated AML patients was significantly lower than that from the bone marrow of 30 normal controls (3059 +/- 1392) vs (7432 +/- 1261) (P < 0.01). The mean PDCD5 fluorescence intensity was lower in the marrow granulocytes, monocytes, blast cells, and lymphocytes from untreated AML patients than that from normal (3939 +/- 2121) vs (8367 +/- 1045); (3156 +/- 1635) vs (5917 +/- 2329); (2824 +/- 1592) vs (3998 +/- 2106); (1474 +/- 816) vs (3355 +/- 2042) respectively, (all P < 0.01). Western blot analysis demonstrated that PDCD5 expression was significantly decreased in the AML cells, as compared with normal cells. It is concluded that PDCD5 expression in MNC in untreated AML patients is lower than that in the normal. PDCD5 expression in the marrow granulocytes, monocytes, blast cells, and lymphocytes of untreated AML patients is significantly lower than that in the normal. It suggests that the abnormally low expression of PDCD5 may be involved in the pathogenesis of AML.
Apoptosis ; physiology ; Apoptosis Regulatory Proteins ; metabolism ; Bone Marrow Cells ; metabolism ; Humans ; Leukemia, Myeloid, Acute ; metabolism ; pathology ; Neoplasm Proteins ; metabolism