Proposed revised criteria for the classification of acute myeloid leukemia. A report of the French-American-British Cooperative Group.
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ABSTRACT: Over-expression of vascular endothelial growth factor A (VEGF-A) is correlated with leukemia metastasis. VEGF-A acts by binding to its membrane receptors R1 and R2 present in soluble forms (sVEGFR1, sVEGFR2) with different functions. sVEGFR could inhibit VEGF-A bioactivities, associated with favorable prognosis in solid tumors. However, its role is obscure in central nervous system leukemia (CNSL). The aim of this study was to investigate sVEGFR1, R2 as biomarkers in CNSL. Paired cerebrospinal fluid (CSF) and serum samples were collected from 35 leukemia cases with or without CNS metastasis. Levels of sVEGFR1 and sVEGFR2 in both CSF (sVEGFR1(CSF), sVEGFR2(CSF)) and serum (sVEGFR1(Serum), sVEGFR2(Serum)) were detected by ELISA. Other risk factors related to CNSL prognosis were also analyzed. sVEGFR(Serum) levels were 2.54-fold (sVEGFR1) and 25.6-fold (sVEGFR2) higher than sVEGFR(CSF) in both leukemic groups. sVEGFR1(CSF) in CNSL were 33 % higher than in the non-CNSL, and the levels of sVEGFR2(CSF) and sVEGFR2(Serum) had the same trend. Elevated sVEGFR1(CSF) and sVEGFR2(CSF) is closely correlated with blood-brain barrier (BBB) values and WBC(CSF) that is an indicator of CNSL disease burden. Cox regression analysis showed that the sVEGFR2(CSF) had a positive effect on event-free survival. Our data suggest that sVEGFR2(CSF) may be more potent than sVEGFR1(CSF) in predicting the outcome of leukemia patients, the balance between sVEGFR2(CSF) and VEGF-A(CSF) levels might be crucial for the progression of CNSL.Journal of Neuro-Oncology 02/2013; DOI:10.1007/s11060-013-1066-x · 2.79 Impact Factor
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ABSTRACT: Metastasis to the central nervous system (CNS) is an obstacle for leukemia treatment, the mechanisms of which remain to be elucidated. VEGF-A and VEGF-C are suspected to participate in this process. Paired of cerebrospinal fluid (CSF) and serum samples were collected from leukemia and control cases. Levels of VEGF-A and VEGF-C in both CSF (VEGF-A(CSF), VEGF-C(CSF)) and serum (VEGF-A(Serum), VEGF-C(Serum)) were detected by ELISA. Our data show that higher levels of VEGF-A(CSF) are closely related to CNS leukemia (CNSL), and VEGF-A(CSF) may be a better predictor than the other risk factors elucidating the pathogenesis and development of CNSL.Leukemia research 11/2012; 37(4). DOI:10.1016/j.leukres.2012.10.008 · 2.69 Impact Factor
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ABSTRACT: The NB4 promyelocytic cell line exhibits many of the characteristics of acute promyelocytic leukemia blast cells, including the translocation (15 : 17) that fuses the PML gene on chromosome 15 to the RARα gene on chromosome 17. These cells have a very high fibrinolytic capacity. In addition to a high secretion of urokinase, NB4 cells exhibit a 10-fold higher plasminogen binding capacity compared with other leukemic cell lines. When tissue-type plasminogen activator was added to acid-treated cells, plasmin generation was 20-26-fold higher than that generated by U937 cells or peripheral blood neutrophils, respectively. We found that plasminogen bound to these cells can be detected by fluorescence-activated cell sorting using an antiplasminogen monoclonal antibody that specifically reacts with this antigen when it is bound to cell surfaces. All-trans retinoid acid treatment of NB4 cells markedly decreased the binding of this monoclonal antibody. This cell line constitutes a unique model to explore plasminogen binding and activation on cell surfaces that can be modulated by all-trans retinoid acid treatment.BioMed Research International 10/2012; 2012:984589. DOI:10.1155/2012/984589 · 2.71 Impact Factor