The Expression And Significance Of Hif-1α In Patients With Acute Leukemia And Its Relationship With Igf-i

Background and ObjectiveRapid proliferation of tumor cells induces increasement of oxygen consumption and makes them in hypoxia.Normal hematopoiesis happens in the environment of relative hypoxia,while leukemia cell proliferation and normal hematopoiesis inhibition make hypoxia more serious.Hypoxia-inducible Factor-1(HIF-1) is an important transcription factor of regulation and cotrol tumor hypoxia effect.HIF-1αis the only oxygen adjustment unit and determine the activity of HIF-1.HIF-1αprobably involves the regulation and control the transcription activity of about sixty kinds of downstream taget genes that include vascular endothelial growth factor (VEGF),erythropoietin(EPO)and so on.What's more,it plays an important role in promoting angiogenesis,maintening cell survival and glucose metabolizing and is closely linked to tumor development and invasion,tumor cell proliferation and apoptosis.IGFs is a kind of polypeptide growth factor which has mutiple biological activity and can promote cell multiplication and differentiation and angiogenesis. IGF-I is an important member of the family.A great number of evidences suggest that IGF-1αregulate and control the growth and hyperplasia of a variety of carcinomas.Tests suggest that the expressions of HIF-1αand IGF-I are positive correlation in glioma,esophageal squamous cell carcinoma,primary liver cancer, multiple myeloma.The expressions of HIF-1αand IGF-I in bone marrow mononuclear cells of acute leukemia were detected by the means of immunohistochemical staining in the research.The correlation between them and the patients' clinical manifestations and the inter-relationship between the two were analyzed.Then the possible role of HIF-1αand IGF-I in proliferation and inflitration of acute leukemia cell were explored.Materials and Method1.Patients:All the samples were obtained from the patients treated in the Hemologic Department of the First Affiliated Hospital of Zhengzhou University through April of 2008 to April of 2009.The acute leukemia were diagnosed by cell morphology,histological chemistry,cellular immunology and(or) molecular genetics. (1) De novo leukemia group(n=49):acute myelogenous leukemia(n=31),acute lymphocytic leukemia(n=18);(2) AL-CR group:bone marrow samples from patients (n=29) who reached CR after chemotherapy.(3)The control group:bone marrow samples from non-maligant hematological diseases(n=12).2.Sample processing:bone marrow mononuclear cells were separated from 2ml bone marrow of untreated Acute Leukemia patients and control patients.The BMNC were load on slides and detected by immunocytochemcal staining for the expression of HIF-1αand IGF-1.3.Statistical analysis:The data were analyzed with Fisher's exact test and Spearman correlation by SPSS13.0 and the standard of statistic significance was established asα=0.05.Results1.The expression of HIF-1αin control group was weak or negative.HIF-1αin initialed novo AL was positively or strong positively expressed in nuelear or cytoplasm,The positive rate was 74.19%in AML,72.22%in ALL.There was no significanee between the positive rate of AML and ALL(P＞0.05).The positive rate of HIF-1αin AL-CR was 20.69%and 16.67%in the control.There was no significance between the positive rate of AL-CR and the control(P＞0.05).The expression of HIF-1αin AML and ALL was significantly higher than that in AL-CR and the control respectively(P＜0.05).2.The expression of IGF-I in control group was weak or negative.IGF-I in initialed novo AL was positively or strong positively expressed in nuelear or cytoplasm,The positive rate was 70.97%in AML,66.67%in ALL.There was no signifieanee between the positive rate of AML and ALL(P＞0.05).The positive rate of IGF-I in AL-CR was 17.24%and 16.67%in the control.There was no significance between the positive rate of AL-CR and the control(P＞0.05).The expression of IGF-I in AML and ALL was significantly higher than that in AL-CR and the control respectively(P＜0.05).3.There was a positive correlation between HIF-1αand IGF-I(r=0.643, P＜0.01).4.There was no significant correlation between the level of HIF-1α,IGF-I and patient's sex,age,WBC.There was a manifest correlation between the level of HIF-1α,IGF-I and infiltration of Leukemia.Conclusion1.Both HIF-1αand IGF-I expressions were significantly higher in AML and ALL than that in control and AL-CR,which suggested that HIF-1α,IGF-I participate in leukernogenesis through promoting malignant proliferation of leukemia cells.2.this study also showed that HIF-1αlevel correlated with IGF-I positively, which suggests that the synergistic action between HIF-1αand IGF-I process development of acute leukemia.3.There was a manifest correlation between the expression of HIF-1α,IGF-I and infiltration of Leukemia,which suggested that the overexpression probably induces transcription of target gene such as VEGF and through the synergistic action.