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Both all-trans retinoic acid (ATRA) and arsenic trioxide ([As.sub.2][O.sub.3]) have proven to be very effective in obtaining high clinical complete remission (CR) rates in acute promyelocytic leukemia (APL), but they had not been used jointly in an integrated treatment protocol for remission induction or maintenance among newly diagnosed APL patients. In this study, 61 newly diagnosed APL subjects were randomized into three treatment groups, namely by ATRA, A[s.sub.2][O.sub.3], and the combination of the two drugs. CR was determined by hematological analysis, tumor burden was examined with real-time quantitative RT-PCR of the PML-RAR[alpha] (promyelocytic leukemia-retinoic acid receptor [alpha]) fusion transcripts, and side effects were evaluated by means of clinical examinations. Mechanisms possibly involved were also investigated with cellular and molecular biology methods. Although CR rates in three groups were all high ([greater than or equal to] 90%), the time to achieve CR differed significantly, with that of the combination group being the shortest one. Earlier recovery of platelet count was also found in this group. The disease burden as reflected by fold change of PML-RAR[alpha] transcripts at CR decreased more significantly in combined therapy as compared with ATRA or [As.sub.2][O.sub.3] mono-therapy (P < 0.01). This difference persisted after consolidation (P < 0.05). Importantly, all 20 cases in the combination group remained in CR whereas 7 of 37 cases treated with mono-therapy relapsed (P < 0.05) after a follow-up of 8-30 months (median: 18 months). Synergism of ATRA and A[s.sub.2][0.sub.3] on apoptosis and degradation of PML-RAR[alpha] oncoprotein might provide a plausible explanation for superior efficacy of combinative therapy in clinic. In conclusion, the ATRA/A[s.sub.2][O.sub.3] combination for remission/ maintenance therapy of APL brings much better results than either of the two drugs used alone in terms of the quality of CR and the status of the disease-free survival.

We investigate the role of mutations of receptor tyrosine kinases as well as their downstream scaffold molecules in leukemogenesis of acute myeloid leukemia (AML) in Chinese patients. Genes of interest included FLT3, PDGFRβ, KDR, CSF2Rβ, SOCS1, PIAS3 and SHIP. The coding sequence of these genes was analysed by the reverse transcription-polymerase chain reaction to search novel mutations. A novel mutation (A > T, Q1154L) of SHIP (1 of 192, 0.52%) was identified and another novel mutation (C > T, R685C) of PDGFRβ (2 of 192, 1.04%). In addition, FLT3 mutations were seen in three of five patients with AML following myelodysplastic syndrome (60%) and 39 of 268 (14.6%) de novo AML patients (P < 0.05). No mutations were found in the coding sequence regions of KDR, CSF2Rβ, SOCS1 or PIAS3. [ABSTRACT FROM AUTHOR]

The paper introduced the concept of critical chain method (CCM) and its network model, presented the structure and implementation of a project scheduling management system based on Internet technology. This system adopts critical chain method and group decision support system (GDSS) as the management basis, and forms a mixed structure including C/S and B/S. [ABSTRACT FROM AUTHOR]

Objective: To investigate the significance of mutation and single nucleotide polymorphism (SNP) of class III receptor tyrosine kinases such as PDGFRbeta and SHIP in acute myeloid leukemia (AML) patients., Methods: Screening of the mutation and SNP of PDGFRbeta and SHIP by genomic PCR, RT-PCR, directly sequencing and Mass-ARRAY system was carried out in 273 AML patients., Results: The mutations of PDGFRbeta R685C and SHIP Q1153L were detected for the first time in AML patients. The positivity ratio was 0.73% and 0.36% respectively., Conclusion: The mutations of PDGFRbeta R685C and SHIP Q1153L may contribute to leukemogenesis of AML.

Objective: To observe the effects of inhibiting stromal cell derived factor-1 (SDF-1) expression by RNA interference (RNAi) on adhesion and drug sensitivity of Jurkat cells co-cultured with bone marrow stromal cells., Methods: SDF-1 specific short hairpin RNA (shRNA) expressing plasmid was transferred into cultured human acute leukemic bone marrow stromal cells, positive clones were isolated by screening G418 resistance (Group A) , SDF-1 protein level in culture supernatant was detected by enzyme-linked immunosorbent assay (ELISA). The adhesion rates to bone marrow stromal cells layer and the drug sensitivity to doxorubicin of co-cultured Jurkat cells were detected by cell counting and MTT assay, respectively. The un-transfected bone marrow stromal cells of acute leukemia patient (Group B) or normal subject (Group C) were taken as control., Results: The level of secreted SDF-1 protein (pg/10(5) cells/week) in the supernatants of Group A, B and C were 1920 +/- 205, 12,370 +/- 1355 and 6620 +/- 770, respectively. Of co-cultured Jurkat cells in Group A, B and C, the adhesion rates after 24 h co-culturing were (28.8 +/- 2.6)%, (57.4 +/- 3.8)% and (45.2 +/- 4.0)%, respectively, and the IC50 values of doxorubicin were 585, 6162 and 1758 nmol/L, respectively., Conclusion: Down-regulating SDF-1 expression of bone marrow stromal cells by RNAi reduces adhesion rates and enhances drug sensitivity to doxorubicin of their co-cultured Jurkat cells.

Objective: To study the effects of RNA interference inhibiting stromal cell derived factor-1 (SDF-1) expression on the proliferation and apoptosis of co-cultured Jurkat cells., Method: Inhibition of SDF-1 expression by RNA interference (RNAi) was achieved by transferring SDF-1 specific short hairpin RNA (shRNA) expressing plasmid into cultured human acute leukemic bone marrow stromal cells. Resistant clones were obtained by G418 selection (group A). The concentration of SDF-1 protein in culture supernatant was detected by enzyme-linked immunosorbent assay (ELISA). The population double time (PDT), cell cycles, apoptosis rates and the expressions of PCNA, Bcl-2/Bax, Fas/FasL of co-cultured Jurkat cells were detected by cells counting, flow cytometry. TdT-mediated dUTP nick-end labelling (TUNEL) and immunocytochemistry (ICC), respectively. The un-transfected acute leukemic (group B) and normal (group C) bone marrow stromal cells were taken as controls., Results: The content of SDF-1 protein in supernatant of group A\[(384 +/- 41) pg/ml] was significantly lower than that in group B[(2474 +/- 271) pg/ml] or group C[(1324 +/- 154) pg/ml]. As group A compared with group B and group C, the PDT of co-cultured Jurkat cells was prolonged (group A: 42 h, vs group B: 29 h, group C: 33 h), and G(0)/G(1) stage cells increased [group A: (28.47 +/- 2.39)%, vs group B: (19.43 +/- 2.80)%, group C: (27.15 +/- 2.07)%], S stage cells decreased [group A: (25.57 +/- 1.90)%, vs group B: (74.48 +/- 3.23)%, group C: (60.99 +/- 2.33)%], G(2)/M stage cells increased [group A: (45.96 +/- 3.24)%, vs group B: (6.09 +/- 1.96)%, group C: (11.86 +/- 1.98)%], the apoptosis rate increased [group A: (15.2 +/- 0.8)%, vs group B: (5.4 +/- 0.7)%, group C: (9.5 +/- 0.4)%], and the expressions of PCNA, Bcl-2, Fas decreased; whereas the expressions of Bax and FasL were increased., Conclusion: The inhibition of SDF-1 expression in bone marrow stromal cells inhibits the proliferation and promotes the apoptosis of co-cultured Jurkat cells.