关键词: 慢性粒细胞白血病, 间充质干细胞, 骨髓间充质干细胞, 免疫逃逸, 基质金属蛋白酶9

Abstract:

BACKGROUND: Chronic myelocytic leukemia had abnormal hematopoietic microenvironment and abnormal immunology. We presumed that mesenchymal stem cells (MSCs) may play an important role in pathological process of chronic myelocytic leukemia.
OBJECTIVE: To investigate biological characteristics of chronic myeloid leukemia hemangioblasts and its regulatory effects, and to compare the differences with bone marrow mesenchymal stem cells (BMSCs) from normal donors.
METHODS: MSCs were isolated from normal donors and BMSCs from patients with chronic myelocytic leukemia. The differences in morphology, phenotype, cell growth and T lymphocyte activation were examined. Obtained cells were cocultured with umbilical cord blood stem cells. The effects on colony formation and differences in relative molecule expression were determined in coculture system.
RESULTS AND CONCLUSION: There were no differences in morphology, phenotype and doubling time of MSCs from patients and normal donors. Inhibitory ability of BMSCs on T cell activation was weakened in chronic myelocytic leukemia patients. In coculture system, suspended cells became more, which indicated that the adherence between hematopoietic stem cells and MSCs was weakened. Simultaneously, protein and RNA levels revealed that matrix metalloproteinase-9 levels increased, and KitL of intercellular adhesion molecule-1 changed from membrane form into soluble form. The results showed that BMSCs of chronic myelocytic leukemia patients were the microenvironment of cell differentiation and development. Its basic mechanisms were the degradation of matrix metalloproteinase-9 on extracellular matrix and split of adhesion molecule. Changes in bone marrow microenvironment support effects on adhesion, proliferation and differentiation of hematopoietic stem cells lead to abnormal proliferation and mobilization of hematopoietic stem cells, decrease sensitivity of cancer cells on immunocytes, resulting in immune escape.