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Objective: Chronic graft-versus-host disease (cGVHD) is a major long-term complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . It is important to study the changes of serum biomarkers expression in patients for early diagnosis and treatment. Methods: The expression levels of five serum protein markers (IL-1b, IL-16, CXCL9, CCL19, CCL17) in patients with or without cGVHD after allo-HSCT were detected by liquid suspension microarray. Results: Compared with the control group without cGVHD, the expression levels of CXCL9 and CCL17 in serum of patients with cGVHD were significantly increased (P<0.05) . CCL17 was correlated with the severity of cGVHD (P<0.001) . CXCL9 was significantly increased in the serum of patients with skin lesion (P<0.01) , and CCL17 was significantly expressed in cGVHD patients with liver as the target organ (P<0.01) . Conclusion: The combination of CXCL9 and CCL17 can be used as serum biomarkers of cGVHD, which has certain reference value in assisting the diagnosis and evaluation of cGVHD severity.
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Doença Enxerto-Hospedeiro , Biomarcadores , Doença Crônica , Transplante de Células-Tronco Hematopoéticas , Humanos , Transplante HomólogoRESUMO
Essentials The pathogenesis of immune thrombocytopenia (ITP) has not been fully clarified. We analyzed the role of anti-αvß3 autoantibody in the pathogenesis of ITP in patients. Anti-αvß3 autoantibody impeded megakaryocyte migration and adhesion to the vascular niche. Anti-αv ß3 autoantibody potentially contributes to the pathogenesis of refractory ITP. SUMMARY: Background The pathogenesis of immune thrombocytopenia (ITP) has not been fully clarified. Anti-αvß3 integrin autoantibody is detected in chronic ITP patients, but its contribution to ITP is still unclear. Objectives To clarify the potential role of anti-αvß3 integrin autoantibody in chronic ITP and the related mechanism. Methods Relationship between levels of anti-αvß3 autoantibody and platelets in chronic ITP patients was evaluated. The influence of anti-αvß3 antibody on megakaryocyte (MK) survival, differentiation, migration and adhesion was assessed, and the associated signal pathways were investigated. Platelet recovery and MKs' distribution were observed in an ITP mouse model pretreated with different antibodies. Result In this study, we showed that the anti-αvß3 autoantibody usually coexists with anti-αIIbß3 autoantibody in chronic ITP patients, and patients with both autoantibodies have lower platelets. In in vitro studies, we showed that the anti-αvß3 antibody had no significant effect on the survival and proliferation of MKs, whereas it decreased formations of proplatelet significantly. Anti-αvß3 antibody impeded stromal cell derived facor-1 alpha (SDF-1α)- mediated migration and inhibited the phosphorylation of protein kinase B. Anti-αvß3 antibody significantly inhibited MKs' adhesion to endothelial cells and Fibrogen. The phosphorylation of focal adhesion kinase and proto-oncogene tyrosine-protein kinase Src induced by adhesion was inhibited when MKs were pretreated with anti-αvß3 antibody. In in vivo studies, we showed that injection with anti-αv antibody delayed platelet recovery in a mouse model of ITP. Conclusions These findings demonstrate that the autoantibody against integrin αv ß3 may aggravate thrombocytopenia in ITP patients by impeding MK migration and adhesion to the vascular niche, which provides new insights into the pathogenesis of ITP.
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Autoanticorpos/imunologia , Autoantígenos/imunologia , Integrina alfaVbeta3/imunologia , Megacariócitos/imunologia , Púrpura Trombocitopênica Idiopática/imunologia , Adolescente , Adulto , Idoso , Animais , Adesão Celular , Movimento Celular , Células Cultivadas , Quimiocina CXCL12/metabolismo , Células Endoteliais/metabolismo , Feminino , Sangue Fetal/citologia , Humanos , Masculino , Megacariócitos/citologia , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Fosforilação , Contagem de Plaquetas , Glicoproteína IIb da Membrana de Plaquetas/imunologia , Proteínas Quinases/metabolismo , Processamento de Proteína Pós-Traducional , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas c-akt/metabolismo , Púrpura Trombocitopênica Idiopática/sangue , Células Estromais/metabolismo , Trombopoese , Adulto JovemRESUMO
WHAT IS KNOWN AND OBJECTIVE: Chemotherapy can increase treatment-related mortality associated with future haematopoietic stem cell transplantation (HSCT) for patients with relapsed/refractory acute myeloid leukaemia (AML). There is usually insufficient time to find a suitable unrelated donor for these patients. We report on the use of decitabine, a DNA methyltransferase inhibitor as a conditioning regimen for a patient undergoing HSCT. CASE SUMMARY: Our patient was a 21-year-old male diagnosed with AML-M1 with 84·5% blast cells and a normal karyotype. His risk stratum was intermediate, without specific mutations of FLT3/ITD, NPM1, CEBPA and C-kit. He underwent successful haploidentical HSCT using decitabine, a conditioning regimen. WHAT IS NEW AND CONCLUSION: We present the first report of a patient with refractory AML (with 58% blast cells) treated successfully with decitabine as a conditioning regimen in haploidentical HSCT.
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Azacitidina/análogos & derivados , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Aguda/terapia , Condicionamento Pré-Transplante/métodos , Antimetabólitos Antineoplásicos/administração & dosagem , Azacitidina/administração & dosagem , Decitabina , Humanos , Masculino , Nucleofosmina , Resultado do Tratamento , Adulto JovemRESUMO
INTRODUCTION: To detect the expressions of drug-resistance related proteins in bone marrow mononuclear cells of acute leukemia (AL) patients using protein microarray and to analyze the clinical value of protein microarray in predicting prognosis of AL patients. PATIENTS AND METHODS: A total of 48 AL patients received chemotherapy were divided into four groups: recurrent acute myeloid leukemia group (R-AML; n=15); AML continue remission group (AML-CR; n = 13); recurrent acute lymphocytic leukemia group (R-ALL; n=13); and ALL-CR group (n=7). Fifteen age-matched patients with non-hematologic disease were used as controls. RESULTS: Expression levels of P-gp, LRP/MVP, BCL-2, GST-π, PCNA, CXCR4 were increased significantly in both AML-R and ALL-R groups (p < 0.05). Besides, LFA-1 and TRAIL-R were also up-expressed significantly in ALL-R group (p < 0.05). In addition, the levels of P-gp, GST-π expressed in AML-R group were higher than those in AML-CR group (p < 0.05) and P-gp, LRP/MVP, GST-π, LFA-1 and CXCR4 in ALL-R were expressed higher than those in ALL-CR group (p < 0.05). CONCLUSIONS: The recurrent of AL were related closely to the over expression of drug resistance-related proteins. Protein microarray can be used in the prediction of AL recurrence and would be beneficial in guiding individual therapy and patient prognosis.
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Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/metabolismo , Resistencia a Medicamentos Antineoplásicos , Leucemia Mieloide Aguda/tratamento farmacológico , Proteínas de Neoplasias/metabolismo , Análise Serial de Proteínas , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Masculino , Seleção de Pacientes , Medicina de Precisão , Valor Preditivo dos Testes , Recidiva , Indução de Remissão , Resultado do TratamentoRESUMO
OBJECTIVE: Our previous study showed that human umbilical cord blood-derived stromal cells (hUcBdSCs) expanded CD34(+) cells in vitro. This study further explored the role of hUcBdSCs in vivo. METHODS: The cultured hUcBdSCs were infused into transplanted haploidentical mice to observe hematopoietic recovery and complications. RESULTS: The engraftment was faster in transplantation with hUcBdSCs than without hUcBdSCs. The numbers of fibroblast (CFU-F), granulocyte/monocyte (CFU-GM), erythrocytic (CFU-E), and megakaryocyte (CFU-Mg) colony-forming units were greater among mice transplanted with hUcBdSCs than without hUcBdSCs. The scoring of graft-versus-host disease was significantly lower in mice that had been subjected to transplantation with hUcBdSCs than without hUcBdSCs. The infused hUcBdSCs migrated to the bone marrow of the recipients. CONCLUSIONS: These data indicated that hUcBdSCs improved hematopoietic reconstitution in haploidentical transplantation in mice.
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Transplante de Células-Tronco de Sangue do Cordão Umbilical , Sangue Fetal/citologia , Hematopoese , Transplante de Células-Tronco Hematopoéticas , Nicho de Células-Tronco , Células Estromais/transplante , Animais , Movimento Celular , Células Cultivadas , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Fibroblastos/transplante , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Histocompatibilidade , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Fatores de Tempo , Quimeras de TransplanteRESUMO
Unmanipulated haploidentical/mismatched related transplantation with combined granulocyte-colony stimulating factor-mobilised peripheral blood stem cells (G-PBSCs) and granulocyte-colony stimulating factor-mobilised bone marrow (G-BM) has been developed as an alternative transplantation strategy for patients with haematologic malignancies. However, little information is available about the factors predicting the outcome of peripheral blood stem cell (PBSC) collection and bone marrow (BM) harvest in this transplantation. The effects of donor characteristics and procedure factors on CD34(+) cell yield were investigated. A total of 104 related healthy donors received granulocyte-colony stimulating factor (G-CSF) followed by PBSC collection and BM harvest. Male donors had significantly higher yields compared with female donors. In multiple regression analysis for peripheral blood collection, age and flow rate were negatively correlated with cell yield, whereas body mass index, pre-aphaeresis white blood cell (WBC) and circulating immature cell (CIC) counts were positively correlated with cell yields. For BM harvest, age was negatively correlated with cell yields, whereas pre-BM collection CIC counts were positively correlated with cell yield. All donors achieved the final product of >or=6 x10(6) kg(-1) recipient body weight. This transplantation strategy has been shown to be a feasible approach with acceptable outcomes in stem cell collection for patients who received HLA-haploidentical/mismatched transplantation with combined G-PBSCs and G-BM. In donors with multiple high-risk characteristics for poor aphaeresis CD34(+) cell yield, BM was an alternative source.