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Objective To explore the effects of injection of wnt3a gene-modified bone marrow mesenchymal stem cells (MSCs) on acute graft-versus-host disease (aGVHD) in a murine allogeneic bone marrow transplantation (allo-BMT) model.Methods C57BL/6 mice were used as the donors and Balb/c mice as the recipients in the murine allo-BMT model.The recipient mice were divided into four groups by random number table method: transplantation control group (group A) (infusion of 5 × 106bone marrow cells via the tail vein of recipient mice); aGVHD group (group B) (infusion of 5 × 106bone marrow cells and 5 × 106 splenocytes via the tail vein of recipient mice); aGVHD + empty vector group (group C) (infusion of 5 × 106 bone marrow cells,5 × 106 splenocytes and 1 × 106 pAd-GFP-transfected MSCs via the tail vein of recipient mice) ; experimental group (group D) (infusion of 5 ×106 bone marrow cells,5 × 106 splenocytes and 1 × 106 wnt3a gene-modified MSCs).The general performance and survival were monitored,the occurrence of aGVHD was observed,the changes of donor T lymphocyte quantity present in the spleen,and interleukin-2 (IL-2) and interferon-γ (IFN γ)levels of the recipient mice were detected in each group after transplantation.Results The survival time of recipient mice in group A was all more than 60 d,and that in groups B,C and D was (19.1 ±6.19),(32.6 ± 19.6) and (47.2 ± 15.6) d,rcspcctivcly.The survival time in group D was significantly longer than in groups B and C (P＜0.05).After the transplant,the aGVHD score points in groups B,CandDwere (8.0±0.41),(6.7±0.29) and (4.0± 1.0),respcctively.The aGVHD score points in group D were significantly less than in groups B and C (P＜0.05),and the pathological grade in group D was significantly reduced.The number and proliferation rate of T lymphocytes were reduced significantly in group D as compared with groups B and C at 3rd and 5th day after transplantation (P ＜ 0.05).The levels of IL-2 and IFN-γ in peripheral blood were decreased significantly in group D as compared with those in groups B and C at 7th,14th,21st and 28th day after transplantation (P＜0.05).The chimeric rate of the murine H-2Kb cells in the bone marrow cells of long-term survival mice was all in the range of 95％ to 100％ 60 d after transplantation.Conclusion The injection of wnt3a gene-modified MSCs can more effectively alleviate aGVHD in murineallo-BMT model,which may be correlated with the Wnt3a overexpression which activating the Wnt/β-catenin signaling pathway of MSCs,thereby inhibiting the early activation and amplification of donor T lymphocytes and the IL-2 and IFN-γ expression.
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Objective To study retrospectively the response and side effects in two groups of patients with untreated multiple myeloma receiving bortezomib-based regimen(VD/VT)and vincristine combined with adriamycin and dexamethasone(VAD).Methods Eighteen patients were enrolled in a group of VD or VT,receving bortezomib 1.0 mh/m2 or 1.3 mg/m2 on days 1,4,8 and 11,along with dexamethasone 20-40 mg on days 1-4(12 cases);or thalidomide 100 mg/d continuously(6 cases). Twenty-four patients treated with VAD entered into a control group,receiving vincristine 0.4 mg/d on days 1- 4,adriamycin 9 mg·m-2·d-1 on days 1-4 and dexamethasone on days 1-4,9-12,17-20,with 28 days as a cycle.Results After bortezomib-based combinations,16 of with 18 patients(88.9%)achieved at least a partial response,including complete response and near complete response in 7 patients(38.9%).Side effects in the VD/VT group were predictable and manageable;they were mainly haematologic, gastrointestinal,and peripheral neuropathic and were more evident during early cycles.The main side reactions in the VAD group were infections.loss of hair and phlebitis.Conclusion Bortezomib-based combinations therapy is an effective and safe induction regimen for newly diagnosed multipli myeloma patients and appears significantly superior to VAD,yielding high response rates even in patients with poor prognostic features.
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Objective To study cytogenetic features of multiple myeloma(MM)cells and the relationship between chromosomal karyotypes and subtype,stage,prognostic parameters and treatment of MM.Methods Karyotyping in patients with MM by 24h short-term bone marrow cell culture and G-banding stain were done.Twenty-two patients were treated with conventional chemotherapy(VAD or MP)and 7 patients with Bortezomib(velcade)chemotherapy.Results There was 37.9% of aberrations in patients with multiple myeloma of 29 cases,and the complex and high complex aberrations were 81.8%.Twenty-two patients with VAD or MP chemotherapy;response rate was 81.2% in normal karyotype group;no response was received in the abnormal karyotypes group(P
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Objective To report a case of psoriasis vulgaris associated with acute myelogenous leukemia(AML)(type M4EO).Methods Clinical data from the patient were collected.Histopathologic examination,and examination of bone marrow and peripheral blood smear were performed.The immunologic types of bone marrow cells were analyzed with FACS.Chromosome and G-banding analyses were carried out with cultured bone marrow cells.Results A33-year-old woman had a history of chronic plaque psoriasis for20years.Her cousin had the same disease history.The patient was treated with various therapeutic regi-mens,most of which were traditional Chinese medicines.Recently the patient suffered from myalgia and chest bone pain,periodic bleeding on gums,fever and so on.The abnormal infantile monocytes and promye-locytes were found with bone marrow smear,and crassitude basophilic granules were noticed in eosinophils.The diagnosis of acute myelogenous leukemia type M4EO was made.The diagnosis was confirmed with the immunologic analysis of born marrow cells with FACS.Chromosome and G-banding analyses revealed her karyotype of46,XX,inv(16)/47,XX,inv(16),+8(2/22).The plaque lesions of psoriasis were regressed after allogeneic bone marrow transplantation and the symptoms of AML were resolved.Conclusion It is the first case report of psoriasis vulgaris associated with acute myelogenous leukemia M4EO which responded to allogeneic bone marrow transplantation.