To describe the health-related quality of life (HRQoL) and fatigue burden among adult patients with immune thrombocytopenia (ITP) in China and determine whether they vary with disease phase. This is a cross-sectional, multi-centre observational study of adult ITP patients and the general population. Participants completed the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). We compared HRQoL and fatigue between ITP patients and the general population, overall and by disease phase (newly diagnosed, persistent, and chronic), using propensity score matching. 203 Patients and 269 members of the general population were recruited. Thirty-six ITP patients (17.7%) were newly diagnosed, 46 (22.7%) were persistent, and 121 (59.6%) were chronic. Compared with the general population, ITP patients had impaired HRQoL and greater fatigue burden. The persistent ITP group showed the largest number of SF-36 scales exceeding the minimally important difference: physical functioning [-10.5; 95% confidence interval (CI) -24.5 to 3.5; P \ 0.001], role physical (-16.7; 95% CI -36.4 to 3.0; P \ 0.001), social functioning (-15.6; 95% CI -34.5 to 3.3; P \ 0.001), and role emotional (-12.1; 95% CI -26.0 to 1.8; P \ 0.001). Chronic ITP patients had the worst FACIT-F scores (36.89 ± 5.21). Higher fatigue severity was associated with lower physical and mental HRQoL. The HRQoL and fatigue burden of Chinese adult patients with ITP vary by disease phase.Persistent ITP patients were the most vulnerable subgroup in terms of HRQoL, while chronic ITP patients bear the heaviest fatigue burden.

Imatinib resistance is an important hurdle in the treatment of chronic myeloid leukemia (CML), and CML patients with this drug resistance are often given a dismal prognosis. In this case report, an imatinib-refractory blast phase CML patient was treated with a combination of imatinib and nilotinib. A complete hematologic response was achieved within 3 months, the drug combination was well tolerated, and there was a relatively long bone-marrow complete remission. These results suggest that combining imatinib and nilotinib treatment may improve the outcome of imatinib-resistant CML patients in the blast phase. We hypothesize regarding the possible mechanism for the effectiveness of the drug combination by reviewing the recent literature.

Purpose: To identify the biological function of phosphoserine aminotransferase 1 (PSAT1) in regulating cell proliferation and apoptosis in multiple myeloma (MM).Methods: The mRNA and protein levels of PSAT1 were determined using quantitative real-time polymerase chain reaction (PCR) and western blotting, respectively. Cell proliferation was measured using CCK-8 assay.Results: PSAT1 mRNA and protein expression levels were significantly increased in MM cell lines when compared to control cells. Moreover,  downregulation of PSAT1 inhibited MM cell proliferation and induced cell apoptosis, whereas overexpression of PSAT1 promoted MM cell  proliferation and suppressed cell apoptosis. Further analysis demonstrated that the underlying mechanism was via regulation of PI3K/AKT pathway.Conclusion: The results identified a novel role for PSAT1 in the progression of MM, which may provide a therapeutic and a new anticancer target for the therapy of MM. Keywords: Multiple myeloma, PSAT1, Cell proliferation, PI3K/AKT pathway

This study aims to investigate the relationship between hepatitis C virus (HCV) NS3/4A and endogenous interferon regulatory factor-3 (IRF-3). The localization of endogenous IRF-3 protein before and after virus infection was analyzed by immunofluorescence assay (IFA). IFA results revealed that the synergistic action of transfection and HCV virus infection could more effectively reduce the nuclear translocation of endogenous IRF-3 in HeLa cells, compared to the activation of Sendai virus infection alone. The highest nuclear translocation of endogenous IRF-3 in transfected HeLa cells occurred at 24 h after Sendai virus infection. Our study was consistent with a published paper, which revealed that HCV NS3/4A protease could suppress the activation of IRF-3 and was indispensable in the transcription of interferon (IFN)-α/β.

4943 Myelodysplastic syndromes(MDS) are a heterogeneous group of myeloid neoplasms characterized by cytopenia, dysplasia in one or more cell lines, ineffective haematopoiesis, and increased risk of development of acute myeloid leukemias(AML). The precise mechanism of onset and evolution of MDS has not been clarified. Recently, the ten-eleven translocation 2 (TET2) gene has been found mutated in 15–26% of MDS and AML. The TET2 paralog TET1 catalyzes the conversion of 5-methylcytosine to 5-hydroxymethylcytosine; TET2 shares a homologous domain thought to catalyze this conversion, and is hypothesized to act as a tumor suppressor gene by regulating DNA methylation and epigenetic control of gene expression at critical loci important for myelopoiesis and leukemogenesis. Moreover, the hypomethylating agents 5-azacytidine and decitabine, have demonstrated good perspective in the treatment of high-risk MDS, but their effects might be limited to some patients. Given the effect of TET2 in epigenetic regulation, it is supposed that the status of TET2 gene mutation affect the therapeutic effect of hypomethylating agents related above. Hence, the aim of this study was to determine the clinical characteristics of Chinese patients with TET2 mutations and the vitro effect of 5-azacytidine and decitabine on CD34+Lin−bone marrow cells from patients with or without TET2 gene mutation in MDS and AML with previous history of MDS(AML-MDS). In our study, the entire coding sequence of the TET2 gene (exons 3 to 11) were sequenced. DNA for detection of mutations were from PB or BM samples of 17 MDS(RA 1, RARS 1, RCMD 4, RAEB-1 7 and RAEB-2 4) and 8 AML-MDS patients in our hospital. Among the patients, there were 19 males and 6 females. The median age was 59(46∼83) year old. Cytogenetic analysis was proceeded in 16 patients and abnormal karyotypes were detected in 7 patients. According to IPSS, cytogenetics was favorable in 9, intermediate in 3, unfavorable in 4. All patients were found with one or more TET2 mutation, including 20 frameshift and 57 point mutations. Except 2 mutations in exon 9 and 1 in exon7, others were all in exon 3 or 11. Only 9 mutations were homozygous and others were heterozygous. Both homozygous and heterozygous TET2 mutations were found, suggesting that the presence of wild type allele or residual activity is not protective. A large proportion of frameshift mutations caused stop codons resulting in loss of function while missense mutations may lead to decreased function. In addition, CD34+Lin-bone marrow cells from 4 AML-MDS patients were sorted with immune magnetic beads from MACS and cultured with StemSpan SFEM supplemented of StemSpan CC100. Decitabine and 5-azacytidine were respectively employed with concentration of 0. 1, 0. 25, 0. 50μM for 12h, 24h, 48h, and 72h. Cell proliferation was inhibited and apoptosis was induced by both drugs. Three AML-MDS patients had previously been treated with decitabine and LD AraC for 1 to 3 cycles. More observation is needed to evaluate if presence of TET2 mutation represent a negative predictor of response to demethylating agents. In conclusion, our preliminary data showed that high proportion of Chinese MDS and AML-MDS patients carried TET2 mutation, of which most showed heterozygous status and involved exon 3 or 11. Decitabine and 5-azacytidine might have effects on CD34+Lin− bone marrow cells from AML-MDS patients in vitro. Disclosures: No relevant conflicts of interest to declare.