Clinical Characteristics and Karyotype Analysis of Myelodysplastic Syndrome Patients with TP53 mutation / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical characteristics of myelodysplastic syndrome (MDS) with TP53 mutant and the relationship between TP53 mutation and monosomal karyotype in MDS patients.@*METHODS@#The TP53 mutations in 102 patients with de nove MDS were retrospectively analyzed, and the clinical features of the TP53 mutation group and the non-mutation group were compared. The relationship between TP53 mutation and karyotype, especially monosomal karyotype was analyzed.@*RESULTS@#Fifty-two out of the 102 MDS patients were male and 50 were female, the median age was 59.5 (23-83) years old. The mutational frequency of TP53 was 12.7%, which mostly occurred in patients with MDS-EB. As compared with non-mutation group, the hemoglobin level and platelet count were lower (P=0.001, P=0.033), the LDH level and bone marrow blast ratio were higher in TP53 mutation group (P=0.002, P＜0.001), but the statistical difference of alsolute count of neutrophils and levels of serum ferritin and β2-microglobulin between 2 groups was not found. The karyotype abnormality frequency of patients with TP53 mutation was 90.9%, among them 72.7% was monosomal karyotype. The incidence of monosomal karyotype in the TP53 mutation group was very significantly higher than that in the non-mutation group (P＜0.001). MDS with TP53 mutation and monosomal karyotype appeared in the groups with high and very high IPSS-R risk.@*CONCLUSION@#MDS patients with TP53 mutation have unique clinical features and high incidence of monosomal karyotype, and their overall prognosis is poor.

Effect of umbilical cord blood mesenchymal stem cells on peripheral blood lymphocyte subsets / 中国实验血液学杂志

<p><b>OBJECTIVE</b>This study was aimed to investigate the effect of mesenchymal stem cells (MSCs) on subsets and cytokine secretion of T lymphocytes.</p><p><b>METHODS</b>Umbilical cord blood-derived mesenchymal stem cells (UCBMSCs) were isolated by density gradient and were cultared by amplifying culture. The subsets and cytokine secretion of T lymphocytes were detected by flow cytomety after being co-cultured with UCBMSC.</p><p><b>RESULTS</b>The proliferation of lymphocytes was inhibited. CD4(+)T cell subsets were increased, CD8(+)T cell subsets decreased when co-cultured with UCBMSC; Th1 and Tc1 level significantly reduced, while Th2 and Tc2 level slightly increased.</p><p><b>CONCLUSION</b>The UCBMSC can inhibit the proliferation of lymphocytes, especially CD8(+)T cell subsets. In addition, UCBMSCs can reduce Th1 and Tc1 cells, and increase Th2 and Tc2 cells. UCBMSC may have the clinical application potential for preventing and remedying GVHD.</p>

Supporting Effect of Umbilical Cord Blood-Derived Mesenchymal Stem Cells on CD34+ Cell Proliferation and Its Mechanism / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the ability of UCB-derived MSCs to support the expansion of HSCs ex vivo and the possible mechanisms involved in this process.</p><p><b>METHODS</b>HSCs from UCB were co-cultured with UCB-derived MSCs for 14 days, and then the total number of HSCs and colony-forming units (CFU) were detected. Cytokines levels of MSCs supernatant were analyzed using ELISA.</p><p><b>RESULTS</b>The proliferation rate of HSCs co-cultured with MSCs was significantly higher than that of cultured HSCs alone (P<0.05). Furthermore, the addition of exogenous cytokines to the culture system significantly increased the proliferation rate of HSCs (P<0.05). MSCs had secretion of many cytokines, including GM-CSF, IL-7, IL-8, IL-11, SCF and SDF-1α.</p><p><b>CONCLUSION</b>UCB-derived MSCs as a feeder layer can be an alternative approach for ex vivo expansion of HSCs, and the cytokines by secreted UCB-MSCs may mediate the supportive role of MSC to HSC proliferation.</p>

Induction of dendritic cells with multidrug resistance from K562/MDR1 cells / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To induce the differentiation of K562/MDR1 cells into dendritic cells (DC) with multidrug resistance property.</p><p><b>METHODS</b>K562/MDR1 cells and K562 cells were cultured in the presence of GM-CSF and IL-4 to generate DC and matured by TNF-α. On d14 K562/MDR1-DC and K562-DC cells were harvested and the expressions of CD1a, CD83, CD80, CD86, HLA-ABC and HLA-DR were assessed by flow cytometry (FCM). The antigen presentation function of K562/MDR1-DC and K562-DC was determined by allogenic mixed lymphocyte reaction (Allo-MLR). The expression of P-glycoprotein and the intracellular accumulation of daunorubicin (DNR) were detected by FCM. The sensitivity of K562/MDR1-DC and K562-DC cell to vincristine, adriamycin was measured using MTT assay.</p><p><b>RESULTS</b>Both K562/MDR1 and K562 cells were differentiated into dendritic cells in the presence of cytokine cocktails, showing the morphologic and immunophenotypic characteristics of DC. K562/MDR1-DC more markedly enhanced proliferation of allogeneic lymphocytes in MLR than K562-DC. High level expression of P-glycoprotein and efflux of DNR were demonstrated in K562/MDR1-DC. K562/MDR1-DC showed multidrug resistance property, with higher IC(50) to VCR and ADM than that of K562-DCs.</p><p><b>CONCLUSION</b>K562/MDR1 cells can be differentiated into DC with the presence of cytokines, the induced K562/MDR1-DC cells express high level of P-glycoprotein and acquire the multidrug resistance property.</p>