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ABSTRACT: Neuropilin-1 (NRP-1) is a novel receptor of vascular endothelial growth factor (VEGF) and expressed in endothelial cells and tumor cells. The role of NRP-1 in the growth and progression of leukemia is unknown. Here we studied the mRNA expression and effect of NRP-1 in leukemic cells. Our results showed that NRP-1 mRNA was expressed in six of seven leukemic cell lines and primary leukemias derived from all 24 patients with acute myeloid leukemia (AML). Reduced NRP-1 expression by RNA interference led to a decrease of VEGF-mediated mitogenic and migration responses in acute myeloid leukemic cell line HEL. Increased NRP-1 expression was directly correlated with the blast percentage in both peripheral blood and bone marrow of AML patients. Our data demonstrated that a higher level of NRP-1 mRNA was expressed in leukemias and NRP-1 promoted proliferation and chemotaxis of leukemic cells in response to VEGF. Inhibition of NRP-1 functions may provide a new therapeutic strategy for treatment of AML.
Leukemia & lymphoma 03/2008; 49(2):331-8. · 2.40 Impact Factor
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ABSTRACT: This study was aimed to investigate the expression of neuropilin-1 (NRP-1) and NRP-2 mRNA in myeloid leukemia cells and the effect of NRP-1 on cell proliferation and migration. The expressions of NRP-1 and NRP-2 mRNA in bone marrow mononuclear cells of 24 patients with acute myeloid leukemia and in 7 myeloid leukemic cell lines (HL-60, KGIa, NB4, U937, HEL MEG01 and K562) were detected by RT-PCR. The effects of NRP-1 interfered with siRNA on proliferation and migration in leukemic cell line HEL were examined by MTT and migration test. The results showed that the expression of NRP-1 mRNA was found in bone marrow mononuclear cells (BMMNCS) of 24 AML patients, the positive rate was 100% and significantly higher than that in control group (positive rate 67%). The expressions of NRP-2 mRNA were seen in 79% AML patients and in 67% health control, there was no significant difference between them. The increased NRP-1 expression was directly correlated with the blast percentage in both peripheral blood and bone marrow of AML patients (r=05, r=0.4, p<0.05). The expressions of NRP-1 and NRP-2 mRNA were observed in 6/7 and 3/7 myeloid leukemic cell lines respectively. After HEL cells were transfected with siRNA for 24 hours, the expression levels of NRP-1 mRNA and protein decreased obviously. Under VEGF action, the cell number in control group significantly increased, while the cell proliferation in interfered group had been not changed. After being transfected for 24 hours, the migration in interfered group decreased significantly. It is concluded that the higher level of NRP-1 mRNA is expressed in bone marrow mononuclear cells of leukemia patients and plays a pivotal role in proliferation and migration of myeloid leukemic cells. Inhibition of NRP-1 functions may provide a new therapeutic strategy for AML.
Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 12/2007; 15(6):1150-5.
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ABSTRACT: Meisoindigo, an active compound of a Chinese anti-leukemia medicine, has been effectively used in the treatment of chronic myelogenous leukemia (CML). Increasing evidences have demonstrated that angiogenesis is an important pathobiologic feature of CML. The anti-angiogenesis effect of meisoindigo on CML is unknown. In this study, we determined the effects of meisoindigo on the apoptosis, adherence and differentiation of endothelial cells as well as the secretion of vascular endothelial growth factor (VEGF) by CML cells. We found that VEGF level, measured by enzyme-linked immunosorbent assay (ELISA), was higher in bone marrow plasma from CML patients compared with the healthy controls (334.83+/-23.09 ng/L versus 102.36+/-38.76 ng/L, P<0.01). CML cell VEGF production was decreased after CML cells were treated with 10 micromol/L meisoindigo compared with the controls (212.10+/-46.13 ng/L versus 293.75+/-64.79 ng/L, P<0.05). Ten micromole per liter of meisoindigo could induce time-dependent apoptosis of ECV304 cells determined by annexin-V. Treatment of ECV304 cells with meisoindigo for 48 h reduced the number of adherent cells and the expression of VCAM-1 compared with the control cells (43.78+/-9.09% versus 73.51+/-3.21%, P<0.05). Meisoindigo also inhibited tubule formation of HUVECs in an in vitro Matrigel after HUVECs were incubated with meisoindigo for 6 h. Our findings suggest that meisoindigo could inhibit angiogeneic process through decreasing the VEGF secretion in leukemic cells and also through inhibiting the proliferation, adhesion and differentiation of endothelial cells, causing the interruption of a reciprocal stimulatory loop between leukemic and endothelial cells. This effect may contribute to the anti-leukemic effect of this drug.
Leukemia Research 01/2006; 30(1):54-9. · 2.92 Impact Factor
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ABSTRACT: To investigate the clinical and hematological features and identify the prognostic factors associated with short-term survival in primary myelofibrosis (PMF) patients under 45 years old.
The clinical manifestations, laboratory parameters, and survival were retrospectively analyzed in 56 PMF patients under 45 years old. Univariate analysis of prognostic factors was performed using Logrank test and multivariate analysis using COX model.
Of the 56 patients, 27 were males and 29 females. The range of age was from 20 to 45 years (median 38 years). 84% of the patients were anemic and 66% Hb < 100 g/L. 32% of the patients had constitutional symptoms including fever, night sweats and weight loss. The median survival was 69 months (95% CI 11-127). By univariate analysis, Hb < 100 g/L, platelet count < 100 x 10(9)/L, WBC < 10 x 10(9)/L, constitutional symptoms and the duration from first signs to diagnosis < or = 6 months were associated with poor prognosis. By multivariate analysis, only Hb < 100 g/L and constitutional symptoms were independently associated with short survival. With these two adverse prognostic factors, the patients could be separated into a high risk and a low risk groups, and the median survivals were 16 and 88 months, respectively (P < 0.001). Using these two factors to predict the less than 3-years survival for individual patient, the sensitivity, specificity and positive predictive value were 67%, 100% and 100%, respectively.
Hb < 100 g/L and constitutional symptoms in PMF patients under 45 years old were significantly associated with short survival and poor prognosis. These two prognostic factors enabled to separate patients into a high and a low risk groups. The survival of high-risk patients was less than three years.
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 05/2005; 26(5):281-4.
