The soluble VEGF receptor 1 and 2 expression in cerebral spinal fluid as an indicator for leukemia central nervous syste
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LABORATORY INVESTIGATION
The soluble VEGF receptor 1 and 2 expression in cerebral spinal fluid as an indicator for leukemia central nervous system metastasis Yue-Ting Tang • Fang Jiang • Li Guo Meng-Ya Si • Xiao-Yang Jiao
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Received: 6 October 2012 / Accepted: 4 February 2013 / Published online: 12 February 2013 Ó Springer Science+Business Media New York 2013
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 (sVEGFR1CSF, sVEGFR2CSF) and serum (sVEGFR1Serum, sVEGFR2Serum) were detected by ELISA. Other risk factors related to CNSL prognosis were also analyzed. sVEGFRSerum levels were 2.54-fold (sVEGFR1) and 25.6fold (sVEGFR2) higher than sVEGFRCSF in both leukemic groups. sVEGFR1CSF in CNSL were 33 % higher than in the non-CNSL, and the levels of sVEGFR2CSF and sVEGFR2Serum had the same trend. Elevated sVEGFR1CSF and sVEGFR2CSF is closely correlated with blood-brain barrier (BBB) values and WBCCSF that is an indicator of CNSL disease burden. Cox regression analysis showed that the sVEGFR2CSF had a positive effect on event-free survival. Our data suggest that sVEGFR2CSF may be more potent than sVEGFR1CSF in predicting the outcome of leukemia patients, the balance between sVEGFR2CSF and VEGF-ACSF levels might be crucial for the progression of CNSL.
Y.-T. Tang F. Jiang L. Guo M.-Y. Si X.-Y. Jiao (&) Department of Hematology Laboratory, First Affiliated Hospital of Shantou University Medical College, 57 Changping Road, Shantou 515041, Guangdong, China e-mail: [email protected]
Keywords sVEGFR1 sVEGFR2 Central nervous system leukemia Cerebrospinal fluid Serum
Introduction Angiogenesis is essential for tumor growth and metastasis, and is controlled by the balance between positive and negative regulators. Vascular endothelial growth factor (VEGF) expression represents the angiogenic switch which may confer a metastatic potential to tumor even at the early stage of growth [1]. Among the VEGF family, VEGF-A is a key player in tumor-induced angiogenesis, its over-expression has been found in most tumor types [2]. In leukemia, VEGF-A is an independent prognostic factor for treatment outcome in acute myeloid leukemia (AML) [3]. Clinical data shows that elevated plasma levels of VEGF are associated with a reduced survival time and lower complete remission (CR) rates [4]. VEGF acts by binding to specific tyrosine kinase receptors: VEGF receptor 1 (VEGFR1)/Flt-1, VEGFR2/Flk-1, and VEGFR3/Flt-4. VEGF has an autocrine r
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