The Clinical Efficacy of Haploidentical Hematopoietic Stem Cell Transplantation by Using Parental Donors in Patients with Thalassemia / 中国实验血液学杂志

OBJECTIVE@#To analyze the clinical efficacy of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) by using parental donors on thalassemia patients.@*METHODS@#The 13 thalassemia patients treated by haplo-HSCT using parental donors in our hospital from July 1, 2016, to July 1, 2020 were retrospectively reviewed. Hematopoiesis reconstitution, the incidence of GVHD, infections and the long-term survival of the patients were analyzed.@*RESULTS@#Twelve of the 13 patients were successfully implanted, the success rate of implantation was 92.3%. The median time of neutrophil and platelet engraftment was 12.5 days (range, 9-22 days) and 21 days (range,12-34 days), respectively. One patient achieved primary graft failure. Three (25%) patients developed to acute GVHD (aGVHD) and achieved complete remission after treatment. Chronic GVHD developed in three (25%) patients, one of them was extensive and under treatment, while one patient developed to severe bacterial infection (7.7%). CMV viremia was diagnosed in two patients (15.4%). There were no patients developed to CMV disease. Three (23.1%) patients achieved EB viremia after transplantation, one of them developed to EBV-related lymphocytic proliferative disease, while there were no patients showed invasive fungal infection. At the last follow-up, all patients survived, twelve of them were free from transfusion dependency. There were no transplant-related deaths. Projected overall and thalassemia-free survival at three years was 100% and 92.3%, respectively.@*CONCLUSION@#The transplant protocol of haplo-HSCT by using parental donors in patients with thalassemia has reliable source of donors, high incidence of successful implantation and low incidence of GVHD, which can be used as an effective way to increase the source of donors in children with thalassemia.

Plasma MiR-181b and MiR-194 As Biomarkers for Acute Graft- Versus-Host Disease and Significance of Their Changes / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical correlation of expression level changes of miR-181b and miR-194 to the pathogenesis of acute graft-versus-host disease (aGVHD), and determine plasma miR-181b and miR-194 as the potential biomarkers for aGVHD.@*METHODS@#The plasma samples were collected from 31 patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) at before HSCT, 15 days after HSCT and onset of aGVHD. The expression levels of miR-181b and miR-194 were detected by quantitative real-time PCR. Receiver-operating characteristic (ROC) curves and the area under the ROC curve (AUC) were used to assess the sensitivity and specificity of miRNA biomarkers for the diagnosis of aGVHD.@*RESULTS@#MiR-181b and miR-194 downregulated after treatment were significantly upregulated in the plasma at onset of aGVHD (P0.05). The expressions of plasma miR-181b and miR-194 collected on day 15 after HSCT were significantly upregulated in the patients with aGVHD in comparison with non-GVHD patients (P<0.05). Moreover, these elevated miRNAs were detected before aGVHD. The AUC of miR-181b predicting aGVHD was 0.91±0.05 (specificity was 0.94, sensitivity was 0.69). The AUC of miR-194 predicting aGVHD was 0.91±0.06 (specificity was 0.94, sensitivity was 0.77).@*CONCLUSION@#MiR-181b and miR-194 may serve as early biomarkers for the diagnosis and prognosis of aGVHD.

Expression of DNA methyltransferase in myeloma U266 cells and its significance / 中国实验血液学杂志

In order to study the activity and gene expression of DNA methyltransferase (DNMT) on U266 myeloma cells and to analyze their significance, the activity of DNMT was detected by ELISA, and the expressions of DNMT1, DNMT3a and 3b were analyzed by RT-PCR. U266 cells were treated by phenylhexyl isothiocyanate (PHI), and the change of activity and gene expression of DNMT were determined. The results indicated that the activity and expression of DNMT in U266 myeloma cells were higher, compared with normal control. After being treated by different concentration of PHI, U266 cells were driven into apoptosis and the activity of DNMT decreased obviously and the mRNA level of DNMT declined. It is concluded that the activity and gene expression of DNMT on U266 myeloma cells are higher, and DNMT may be a new therapeutic target of multiple myeloma.

Inhibitory effect of phenylhexyl isothiocyanate on notch signaling of multiple myeloma cells in vitro / 中国实验血液学杂志

In order to investigate the mechanisms of phenylhexyl isothiocyanate (PHI) inhibiting the proliferation of multiple myeloma cell RPMI8226 in vitro, the RPMI8226 cells were co-cultured with PHI of various concentrations. The inhibition of proliferation was measured by MTT test and the cell apoptosis was assayed by DAPI staining. The changes of Notch1, Jagged2, BCL-2 and p-Akt proteins in the PHI-treated cells were detected by Western blot. The results showed that PHI inhibited RPMI8226 cell proliferation in certain concentration range and induced their apoptosis. The inhibiting effect caused by PHI showed a concentration-and time-dependent manner. The PHI decreased expressions of Notch1 and Jagged2 proteins in a concentration-and time-dependent manners, the levels of BCL-2 and p-Akt declined at the same time. It is concluded that PHI can inhibit proliferation of RPMI8226 cells, and induce their apoptosis. The cell apoptosis is associated with the inhibition of Notch signaling and downstream targets BCL-2 and p-Akt proteins of RPMI8226 cells, PHI may be a new Notch signaling inhibitor and a promising therapeutic drug for multiple myeloma.