The Influence Of Over-Expression Of TIMP-2 On The Nude Mice Model With CNSL, Multi-Organ Infiltration And The Studies On Relevant Mechanisms Of Extramedullary Infiltration In Leukemia

【Objects】Acute leukemia always accompany with extramedullary infiltration. Extramedullary infiltration, especially for the central nervous system leukemia, is difficulty for the treatment, and some will be the resource of relapse. But the mechanisms of central nervous system leukemia (CNSL) and leukemic infiltration are not been well elucidated because of the deficient of a good CNSL and extramedullary Infiltration model. According to the studies on the solid tumors, many factors are involved in the infiltration and metastasis of malignant tumor cells, i.e. matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), extracellular matrix metalloproteinase inducer (Emmprin, CD147) and SDF-1/CXCR4 and so on. Do these factors involve in the leukemic extramedullary infiltration. MMP-2 had been reported to play important role in this process. In this assay, we aim to establish a nude mice model with CNSL and multi-organ infiltration using a human monocytic leukemic cell line SHI-1, and investigate the roles of TIMP-2 in leukemic infiltration in nude mice; then study the memechanisms of extramedullary infiltration using a in vitro co-cultured model.【Methods】[Section 1] Balb/C nu/nu mice pre-treated by splenectomy , cytoxan intraperitoneal injection, and sublethal irradiation (SCI nu/nu mice), were transplanted intravenously with 1×10~7 cells of humanmonocytic leukemic cell line SHI-1. Every week one 4-week-old SCI-nu/nu mice were sacrificed, and six 6-week-old mice were sacrificed at day 30 after...