Clinical significance of DLL4, HES1, VEGF-C, VEGFR-2 in the bone marrow of leukemia patients

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Author:
YUAN Xiao-jun(Department of Hematology, First Affiliated Hospital, Baotou Medical College, Baotou 014010, China)
HE Qi-tu(Department of Hematology, First Affiliated Hospital, Baotou Medical College, Baotou 014010, China)
BAI Xue-qin(Department of Hematology, First Affiliated Hospital, Baotou Medical College, Baotou 014010, China)
LI Zhe(Department of Hematology, First Affiliated Hospital, Baotou Medical College, Baotou 014010, China)
LU Yah(Department of Hematology, First Affiliated Hospital, Baotou Medical College, Baotou 014010, China)
LIU Xue-wen(Department of Hematology, First Affiliated Hospital, Baotou Medical College, Baotou 014010, China)
HA N Xuan-mao(Department of Hematology, First Affiliated Hospital, Baotou Medical College, Baotou 014010, China)
MA Hong-jie(Department of Hematology, First Affiliated Hospital, Baotou Medical College, Baotou 014010, China)
ZHANG Dong-xia(Department of Hematology, First Affiliated Hospital, Baotou Medical College, Baotou 014010, China)
Journal Title:
Journal of Leukemia & Lymphoma
Issue:
Volume 20, Issue 09, 2011
DOI:
10.3760/cma.j.issn.1009-9921.2011.09.008
Key Word:
Leukemia;Vascular endothelial growth factor C; Receptors, vascular endothelial growth factor;DLL4;HES1;C ene expression

Abstract: Objective To detect the expression level of DLL4, HES1, VEGF-C, VEGFR-2 mRNA in the bone marrow of leukemia patients and find a new treatment for leukemia with some new principles. Methods 59 patients of leukemia were collected and diagnosed on the basis of clinical manifestations, hemogram, bone marrow morphology, histochemical stain, cytogenetics and flow cytometry. 20 patients with nutritional anemia were chosen as the control group. The bone marrow aspiration were collected. Semiquantitative reverse transcription polymerase chain reaction (RT-PCR) was used to detect the levels of DLL4,HES1, VEGF-C, and VEGFR-2 mRNA. Results The levels of DLJL4, HES1, VEGF-C, VEGFR-2 mRNA in each group with newly diagnosed patients with acute and chronic leukemia were significantly higher than that in the control group (P <0.05). The levels of DLL4, HES1, VEGFR-2 mRNA in remission of acute leukemia were significantly higher than that in control group (P =0.041, 0.016, 0.047). In AML group DLL4 and VEGFR-2, HES1 and VEGF-C, mRNA expression were positively correlated (r =0.424, 0.472, P=0.030, 0.014). In CLL group the HES1 and VEGF-C mRNA expression was positively correlated (r =0.997, P =0.042). The levels of VEGF-C mRNA in acute leukemia patients with extramedullary infiltration were higher than that without extramedullary infiltration (P = 0.022). VEGF-C mRNA expression in AML group and the original cell counts were positively correlated (r = 0.315, P = 0.024). Conclusion These results suggested that the interaction of DLL4, HES1 and VECF-C, VEGFR-2 in the pathogenesis of leukemia may promote the development, metastasis and infiltration of leukemia, and these factors in different types of leukemia and extramedullary infiltration are different.

  • [1]Ridgway J,Zhang G,Wu Y,et al.Inhibition of Dl14 signaling inhibits tumour growth by deregulating angiogenesis.Nature,2006,444:1083-1087.
  • [2]Takeshita K,Satoh M,Ii M,et al.Critical role of endothelial Notchl signaling in postnatal angiogenesis.Circ Res,2007,100:70-78.
  • [3]Weng AP,Ferrando AA,Lee W,et al.Activating mutations of Notch1 in human T cell acute lymphoblastic leukemia.Science,2004,306:269-271.
  • [4]Jundt F,Anagnostopoulos I,F?rster R,et al.Activated notch11 signaling promotes tumor cell proliferation and survival in Hodgkin and anaplastic large cell lymphoma.Blood,2002,99:3398-3403.
  • [5]Zayzafcon M,Abdulkadir SA,McDonald JM.Notch signaling and ERK activation are important for the osteomimetic properties of prostate cancer bone metastatic cell lines.J Biol Chem,2004,279:3662-3670.
  • [6]徐喜慧,贺其图,贾国荣,等.白血病患者骨髓血管新生的研究.白血病·淋巴瘤,2005,14:80-82.
  • [7]贺其图,赵晓华,贾国荣,等.白血病患者骨髓血管新生与Bcl-2蛋白关系的研究.实用癌症杂志,2006,21:376-378.
  • [8]刘学文,贺其图,李志芹,等.COX-2在白血病患者骨髓细胞中表达及与血管新生的关系.中国实验血液学杂志,2009,17:40-42.
  • [9]Jundt F,Schwarzer R,D?rken B,et al.Notch signaling in leukemiasm and lymphomas.Curr Mol Med,2008,8:51-59.
  • [10]Axelson H.Notch signaling and cancer.emerging complexity.Semin Cancer Biol,2004,14:317-319.
  • [11]Chiaramonte R,Calzavara E,Balordi F,et al.Differential regulation of Notch signal transduction in leukaemia and lymphoma cells in culture.J Cell Biochem,2003,88:569 -577.
  • [12]Hajdu M,Sebestyén A,Barna G,et at.Activity of the Notch-signalling pathway in circulating human chronic lymphocytic leukaemia cells.Scand J Immunol,2007,65:271-275.
  • [13]Ohsaka A,Hirota-Komatsu S,Shihata M,et al.Specific association of increased vascular endothelial growth factor expression and its receptors with macrophage differentiation of HL-60 leukemia cells.Biochem Biophys Res Commun,2008,368:543-549.
  • [14]Liersch R,Schliemann C,Bicker R,et al.Expression of VEGF-C and its receptor VEGFR-3 in the bone marrow of patients with acutemyeloid leukaemia.Leuk Res,2008,32:954-961.
  • [15]Nowicki M,Ostalska-NowickaD,Kaczmarek E,etal.Vascularendothelial growth factor C-a potent risk factor in childhood acute lymphoblaatic leukaemiaan immunocytochemical approach.Histopathology,2006,49:170-177.
  • [16]Thurston G, Kitajewski J. VEGF and Delta-Notch:interacting signalling pathways in tumour angiogenesis.Br J Cancer,2008,99:1204-1209.
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