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Background: MMPs and TIMPs play important roles in tumor angiogenesis and invasion. Studies have shown that TIMP-2 has two roles in tumor invasion. However, its role in leukemic infiltration has not been well investigated. This study explored the roles of TIMP-2 in extramedullary infiltration of acute monocytic leukemic SHI-1 cells both in vitro and in vitro., Methods: A retroviral vector carrying the human TIMP-2 cDNA was constructed and transfected into the monocytic leukemic cell line SHI-1. The expression of TIMP-2 in the positive clones was determined. The proliferation of SHI-1 cells was examined by MTT assay. Trans-Matrigel invasion assays were used to investigate the infiltration ability in vitro. SHI-1 cells were intravenously injected into pre-treated nu/nu mice to investigate the infiltration ability feature in vitro., Results: The expression of TIMP-2 on the cell membrane was significantly elevated in SHI-1/TIMP-2 cells. Over-expression of TIMP-2 promoted the cells proliferation and the invasions in vitro. The SHI-1/TIMP-2 cells demonstrated higher infiltration ability when intravenously injected into nu/nu mice., Conclusion: Over-expression of TIMP-2, especially on the cell membrane, may play important roles in promoting the proliferation and infiltration of SHI-1 leukemic cells.

Objective: To study telomerase activity (TA) and its variation in bone marrow mononuclear cells from patients with myelodysplastic syndrome (MDS) at different stages in comparison with normal bone marrow cells and leukemic cells., Methods: The TA was semi-quantitatively determined in mononuclear cells from 20 normal bone marrow samples, 21 patients with MDS at different stages and 32 cases of acute leukemia by using a polymerase chain reaction-enzyme linked immuno-sorben assay (PCR-ELISA) kit., Results: The TA in normal bone marrow cells was in the range of 0 to 0.3 units (U) with a mean of 0.11 +/- 0.08 U. Among them, 3 samples were considered positive in accordance with the standard recommended by the kit's pamphlet. In bone marrow cells from patients with acute leukemia, the TA was ranging from 0 to 0.96 U with a mean value of 0.42 +/- 0.26 U. The positive rate was 78.1% which was significantly different from that in normal bone marrow (BM) (P < 0.01). In case of myelodysplastic syndrome, the average level of TA was 0.27 +/- 0.19 U (ranging from 0 to 0.97 U) with a positive rate of 66.7%. In comparison with normal BM cells, the difference was significant (P < 0.05). Particularly, the MDS high-risk subgroup exhibited a significantly higher activity of telomerase (P < 0.05). In comparison with INT-1 and INT-2 subgroups in MDS patients based on international prognostic scoring system (IPPS), the difference in TA was also significant (P < 0.05). The abnormality in cell karyotype was not correlated with TA., Conclusion: The normal bone marrow cells demonstrate TA at a marginal level while a remarkably increasing level may be seen in acute leukemia patients. The BM cells from MDS patients display a moderate TA among which the high risk MDS subgroup with a poor prognostic IPPS score exhibited markedly higher TA.

Objective: To present a special case with the karyotype and molecular marker of acute myeloid leukemia (AML)-M2 who was induced to complete remission by all-trans retinoic acid (ATRA) alone., Methods: A recently hospitalized young female patient with acute leukemia was initially diagnosed as M3 subtype based on morphological French-American-British (FAB) classification. Karyotype analysis using standard G and R banding techniques and RT-PCR were applied to further define the diagnosis. After primarily cultured bone marrow cells from the iliac aspiration were tested for in vitro induced differentiation, the patient was treated with oral all-trans retinoic acid alone, 60 mg per day until complete remission was achieved. Peripheral blood and bone marrow changes were monitored over the whole treatment course., Results: The characteristic chromosomal aberration for M3, the t(15;17) reciprocal translocation, was not found while a t(8;21) translocation was verified. Furthermore, an amplified product of the AML-1/ETO fusion gene instead of the PML/RAR alpha fusion gene was detected by RT-PCR and the diagnosis was corrected from M3 to M2. Primary cultured bone marrow cells can be fully induced to terminal differentiation after 4 days exposure to ATRA. A hematological complete remission was achieved after 40 days treatment with ATRA as a single therapeutic agent, suggesting an alternative pathway mediating ATRA-induced myeloid differentiation., Conclusion: A leukemia patient with a subtype other than M3, such as M2 in this case, may also be induced to complete remission by the mechanism of ATRA-induced terminal differentiation. This implies that there may be a pathway other than PML/RAR alpha fusion gene product which mediates ATRA-induced myeloid maturation in leukemia cells.