[Recipient lymphopenia state enhances the expansion and anti-leukemia effect of leukemia specific cytotoxic T lymphocytes].

OBJECTIVE: To determine the role of recipient lymphopenia state in the expansion and function of leukemia specific cytotoxic T lymphocytes (CTLs). METHODS: C57BL/6 mice were induced to lymphopenia with 6 Gy total body irradiation. Spleen T cells or leukemia specific T cells from EGFP+ transgenic C57BL/6-EGFP mice were adoptively transferred by intravenous injection. The mice were challenged subcutaneously with 1 x 10(6) FBL3 leukemic cells at day 2 after irradiation. The peripheral WBC count, percentage of EGFP+ cells, subsets of T cells and tumor sizes were monitored. RESULT: Both of the spleen T cell and leukemia specific CTL proliferated efficiently with the percentage of EGFP+ cells of 28. 81% and 42.24%, respectively, after infused into lymphopenic recipients. However, spleen T cells had no anti-leukemia effect regardless of its expansion. In contrast, leukemia specific CTLs showed a more rapid and extensive expansion under the condition of lymphopenia and a enhanced anti-leukemia immunity. CONCLUSION: Transfusion of leukemia specific CTLs under lymphopenia state could be a feasible strategy to expand leukemia specific CTLs and generate favorable anti-leukemia effect in vivo.

[Synergistic inhibitory effect of STI571 in combination with arsenic trioxide on a multidrug-resistant leukemia cell line expressing bcr-abl].

OBJECTIVE: To study the synergistic effect of STI571, an inhibitor of tyrosine kinase in combination with arsenic trioxide (As(2)O(3)) on a multidrug-resistant leukemia cell line expressing bcr-abl. METHODS: The cytotoxic effect of STI571 alone or in combination with different concentrations of As(2)O(3) on both bcr-abl and mdr1 positive leukemia cell line K562-n/VCR was detected by MTT method. RESULTS: The cytotoxic effect of STI571 (1 micromol/L) combined with As(2)O(3) at concentrations 10(-5), 10(-6), 10(-7), 10(-8) mol/L (IC(50) 0.155 micromol/L) on K562-n/VCR cells was significantly higher than that of As(2)O(3) alone (IC(50) 1.879 micromol/L). The synergistic interaction on K562-n/VCR cells increased the cytotoxic effect by 12.1-fold. CONCLUSION: Combination of STI571 with As(2)O(3) has a synergistic inhibiting effect on leukemia cells expressing bcr-abl and mdr1.

[Application of SCID mouse-human leukemia model for leukemia research].

SCID mouse-human leukemia model is an important and useful tool for study on proliferation, differentiation and modulation of leukemic cells. In this article, the establishment of the model, advances in research and application in studies of pathogenesis, cell biology, clinical diagnosis, therapy and assessment of prognosis of leukemia patients are reviewed. The limitations of the model are also commented.

[The reverse effect on drug-resistance against tyrosine kinase inhibitor STI571 in mdr1 and bcr-abl positive leukemic cells].

To explore the possibility of leukemia cell line of both bcr-abl and mdr-1 positive were cross-resistant to tyrosine kinase inhibitor STI571 and its reversal way, the inhibitory effect of STI571 on K562-n/VCR cells was detected with MTT method and reverse effects of CsA, TAM, IFN-alpha and CsA cominated with IFN-alpha were observed. The results showed that K562-n/VCR cell line expressing bcr-abl and mdr1 positive was resistant to STI571, and could be reversed by 5.18, 1.82 and 1.67-fold respectively, when treated with CsA, TAM, and IFN-alpha. It could be reversed by 34.87-fold with combination of half-dose CsA and IFN-alpha. In conclusion, amplification of mdr1 gene may contribute to drug-resistance of bcr-abl positive leukemic cells against STI571. The reversal agents, CsA, TAM and IFN-alpha show obviously reverse effects on drug-resistance. The combination of half-dose of both CsA and IFN-alpha display stronger effect than the full dose of either.