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The Expression Of SDF-1α And Its Receptor CXCR4 In Acute Leukemia And The Relationship With Extramedullary Infiltration

Posted on:2005-01-04Degree:MasterType:Thesis
Country:ChinaCandidate:Z R LiuFull Text:PDF
GTID:2144360125457859Subject:Hematology
Abstract/Summary:PDF Full Text Request
Objective: Stromal cell derived factor-1 a (SDF-1 a ) is a major chemoatractent realeased by marrow stromal cell with homologenous structure. It belongs to the CXC subfamily of chemoine. The specific receptor for SDF-1 a is a G-protein coupled receptor, called CXCR4 or LESTR, Fusion, and play a important role in leukocyte trafficking during inflammation. CXCR4 is expressed on many kinds of heamatopoietic and non-hematopoitic cells and involves in serials of nomal physiological procession such as heamatopoiesis, heamatopoitic stem cell homing, embryogenesis, tissure regeneration or reconstruction and wound healing. SDF-1 a /CXCR4 are also expressed in many malignant tumor and contribute to their metastasis and progressing by promoting the tumor cell proliferation, neoagiogenesis, widespreading and immune-escaping in tumo tissure. There have been many researches to support the function of SDF-1 a /CXCR4 in solid tumor invasion, but seldom report about relationship between the SDF-1 a /CXCR4 and leukemia. The study of hematopoisis stem cell homing found that the malignant CD34+ cell may migrate in respondence of SDF-1 a , so it is speculated that SDF-1 a /CXCR4 may contributed to the migration ofmalignant leukemia cells. Moreover, further studies show that SDF-1 a may stimulating the proliferation of primitive leukocyte cell and may assoiated with extramedullary infiltration or the progresis of leukemia. In order to study the relationship between the SDF-1 a / CXCR4 expression and the extramedullary infiltration, Ensamy link immunation absortent test and flow cytomytry were used to determined the expression of SDF-1 a /CXCR4 in different groups of leukemia.Matiarials and Methods: 1 . According to different criteria, the subjectes were divided into different groups: (1) By FAB criteria, the subjetives were divided into three groups: (1)acute lymphocytic leukemia(ALL)(n=31, male :20, female 11, mean age 23.71 + 19.28 Y) , L, 1, L229, L3 1; (2) ANLL(M4+M5) (n=15, male 9, female 6, mean age 39.67+ 17.52 Y; M4 4, M5 11) and (3)ANLL(non-M4+M5)(n=20, maleS female 10, mean age 33.86+13.85 Y; M13, M213, M33, M6 1); (2)By the number of peripherial blood(PB): (1) high-number PB group(PB>20X 109/L)(n= 31, male 17, female 14, mean age 3 1.64 21. 8 Y), (2) non-high-number PB group (PB 20X 109/L) (n=35, male 17, femalelS, mean age 32.86 19.28Y). (3) By the extramedullary infiltration symdrom: extramedullary infiltation group (n=41, male18, female23, mean age 28.74+ 19. 1 6Y) included ALL 23 cases, ANLL(M4+M5) 11 cases, ANLL (non-M4 +M5) 7 cases. The non-extramedullary infiltation group(n=25, male 14, female 11, mean age 32. 1 3 1 7.35 Y) including ALL 8 cases, ANLL(M4+M5) 4 cases, ANLL(non-M4+M5) 13cases. (4) nomal control group: 10 cases, male 5, female 5, mean age 35.0+12.0 Y. 2. Collecting the bone marrow mononuclear cells and the peropherial blood of all subjectes before treatment, the average level of the SDF-1 a and the mean florencence intencity(MFI) of CXCR4 were respectively determeaned by ELISA and the flow cytometry. 3. Statistical assay: the data were dealed with the SPSS 10.0 statistical software.Results: (1) The SDF-1 a average levels (pg/ml) of the ALL , ANLL(M4+M5), ANLL (non-M4+M5) patients and the normal control group were respetively 1317.87 + 220.76, 1339.79+187.06, 1063.70+190.74, 1908.34 135.55. The levels in three kinds of leukemia patients were lower than that in normal control group. Both levels in ALL and ANLL (M4+M5) groups were higher than that in ANLL(non-M4+M5) group. (2) TheMFI of CXCR4 expression in ALL, ANLL(M4+M5), ANLL(non-M4+M5) groups were respectively 78.47 33.96, 67.21 24.29, 41.66 17.18. CXCR4 expression in ALL and ANLL(M4-t-M5) cells were higher than ANLL(non-M4+ M5) ( P<0.05 ) . There was no signiphicant differences between the ALL and ANLL(M4+M5) groups(P>0.05). CXCR4 expression decreased on the ALL cells when myeloid antigen co-expression (ALL mye+) compared with the ALL cells without the myeloid antigen expression(ALL mye-). (3) The average levels(p...
Keywords/Search Tags:acute leukemia, stromal cell derived factor-1α, CXCR4, extramedullary infiltration, number of peripherial blood
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