Expression Of SDF-1/CXCR4 Axis In Bone Marrow Cells And Its Association With Angiogenesis In Leukemia Patients

Background: leukemia is a malignant desease from the hemopoietic stem cell(HSC), it seriously threatens the health and lives of human beings. As the developing of medical science, the diagnostic technique and the therapeutic efficacy of acute leukemia improved greatly. But now, we still can not clearly understand its nosogenesis, furthermore, the infiltration and invasion of leukemia cells outside the marrow are still the most important reasons for recidivation and the death of patients. Therefore it becomes the emphasis for leukemia to approach the mechanism of its genesis, development and the invasion outside the marrow , and the research for its therapeutics is evenmore important. According to the previous research, leukemia is also an angiogenesis dependent malignant disease. The neoformative micrangiums provide the nutritive material and remove the metabolites. Angiogenesis is an important patho-procedure in the procedure and development of leukemia. Stromal cell Derived Factor-1(SDF-1) and its only receptor CXCR4 may play an important role in the leukemia vis its function of changing the miroenviroment of bone marrow. furthermore, the performance of the SDF-1/CXCR4 axis'biological function may be correlated with the expression of the vascular endothelial growth factor (VEGF) the main factor involved in angiogenesis of leukemia. To approach its nosogenesis means greatly for leukemia treatment and lengthening the disease free survival (DFS).Objective: In his research, Stromal cell Derived Factor-1 (SDF-1 )level and vascular endothelial growth factor (VEGF) in serum, the microvessel density (MVD) of bone marrow, and the expression of CXCR4 in bone marrow cells are detected, on the basis of the association of them, we approach the effect of SDF-1/CXCR4 axis in the angiogenesis of bone morrow in leukemia patients, and provide some new directions in clinical treatment and prognosis-judgement of leukemiaMaterials and Methods: 40 patients with newly diagnosed leukemia were chosen for study objects, 15 patients with diagnosed relieved acute leukemia . all are hospital patients in the Hematology Department of NO. 1 Hospital of Baotou Medical College from October 2006 to February 2008. 31 patients are males and 24 patients are females, from 2.5 to 87 years old, and the average age is 41. They were diagnosed and subgrouped on the basis of clinical manifestation, hemogram, bone marrow manifestation, histochemical stain and flow cytometry. In the control group.15 nutritional anemia people were chosen. 4males and 11 females, from 17 to 55 years old, the average age is 36. During the bone marrow aspiration, obtain bone marrow liquid and biopsy tissue. Detecting SDF-1 and the vascular endolesis growth factor(VEGF) level in serum with ELISA method, detecting bone marrow microvessel density (MVD) with immunohistochemistry method, and the expressiong of CXCR4 in bone marrow cells with flow cytometry.Results: In the AML group SDF-1(2145.21±329.45)pg/mL, the positive rate of CXCR4 expression (60.01±18.5)%;MVD (18.16±4.71) /×400 HPF, VEGF (339.24±83.85) pg/mL; In the ALL groupSDF-1(2549.1±303.4 )pg/mL, the positive rate of CXCR4 expression (70.22±12.73)%,MVD(19.21±2.46)/×400 HPF, VEGF (151.35±33.71) pg/mL; In the CML group SDF-1(1929.72±253.81)pg/mL, the positive rate of CXCR4 expression (40.05±16.69)%;MVD(21.46±2.57)/×400HPF, VEGF (934.98±164.31) pg/mL; In the CRALgroup SDF-1(2070.98±159.98)pg/mL,the positive rate of CXCR4 expression (58.4±11.8)%, MVD(12.31±1.61) /×400 HPF, VEGF(149.58±35.58)pg/mL They are all obviously increased compared with the control group, P<0.05. The coefficients of correlation SDF-1,CXCR4,VEGFare respectively 0.552, 0.553,0.531. (P<0.05). The correlations of them are significant.Conclution: The content of SDF-1 in bone marrow cells in leukemia and the content of CXCR4 in different cell groups such as intial cell,mature lymphocyte,monocyte and granulocyte are highiy expressed. The mostly high expression of these factors is in actue lymphocyte leukemia and relieved leukemia remains to express SDF-1/CXCR4 highly. They have become a kind of method for detecting residual morbid in leukemia . High expression of SDF-1/CXCR4 in bone marrow cells is associated with angiogenesis in leukemia patients.