Study of Decoy Receptor 3 in Hematologic Malignancy

• Main Authors: Dian-Kun Li, 李典錕
• Other Authors: 田蕙芬
• Format: Others
• Language: zh-TW
• Published: 2005
• Online Access: http://ndltd.ncl.edu.tw/handle/92736707427163499703

碩士 === 國立臺灣大學 === 臨床醫學研究所 === 93 === Study of Decoy Receptor 3 Expression in Hematologic Malignancies Decoy receptor 3 (DcR3), a soluble decoy receptor, belongs to the tumor necrosis factor receptor superfamily. Decoy receptor 3 binds Fas ligand, LIGHT, and TL1A, and inhibits Fas ligand- and LIGHT-mediated cell apoptosis and TL1A-medaited angiostatic reaction. DcR3 is expressed in several types of malignant tumors, and is postulated to endow tumor cells to escape immune surveillance. We investigated the bone marrow DcR3 expression in patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), multiple myeloma (MM), and myeloid dysplastic syndrome (MDS), and also evaluated the clinical relevance of DcR3 expression in AML patients. We examined plasma DcR3 levels of bone marrow blood with enzyme-linked immunosorbent assay (ELISA) in 23 healthy bone marrow donors, 95 AML patients, 21 ALL patients, 16 CML patients, 19 MM patients, and 18 MDS patients. Bone marrows from 23 healthy marrow transplantation donors were used as normal controls. The DcR3 protein expression in malignant cells was demonstrated by immunohistochemical staining (IHC). We also examined the DcR3 mRNA expression of leukemic cells by RT-PCR and compared with β-actin expression. The DcR3 levels (mean±S.D.) were 0.42±0.35ng/ml in healthy bone marrow donors, 5.97±18.12 ng/ml in AML patients, 21.95±82.54ng/ml in ALL patients, 0.83±1.48 in CML patients, 0.19±0.31ng/ml in MM patients, 1.40±2.06ng/ml in MDS patients. The IHC showed positive staining of DcR3 in the leukemic cells from the AML patients with elevated serum level of DcR3. The DcR3 mRNA expression of leukemic cells was also correlated with the plasma DcR3 levels. We used the DcR3 level of 1.5ng/ml as cut-off level. There is no significant correlation between DcR3 levels and clinical parameters, except the age, in AML patients. 71 AML patients received induction chemotherapy. The DcR3 levels have no significant association with overall survival in these patients. 49 AML patients achieved hematologic complete remission after induction chemptherpay. The DcR3 levels have no significant association with disease free survival in these patients. We examined the DcR3 levels before and after induction chemotherapy in 7 AML patients who had hematologic complete remission. The DcR3 levels significantly decreased after induction chemotherapy. This is the first study to investigate the DcR3 expression in AML, ALL, CML, MM, and MDS. A significant portion of AML patients showed higher levels of marrow DcR3 than normal controls. In contrast, the marrow levels of DcR3 in MM patients were not increased compared with that in normal controls. The plasma DcR3 level of bone marrow blood may be a potential marker for monitoring of treatment response of AML.