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In recent studies, the tolerable safety profile and positive bone marrow (BM) response suggest a beneficial use of anti-PD-1 agents in the treatment of Myelodysplastic Syndromes (MDS), but the underlying mechanism is still unknown. MDS is mainly characterized by ineffective hematopoiesis, which may contribute to inflammatory signaling or immune dysfunction. Our previous studies focused on inflammatory signaling, and the results showed that S100a9 expression was higher in low-risk MDS and lower in high-risk MDS. In this study, we combine the inflammatory signaling and immune dysfunction. SKM-1 cells and K562 cells co-cultured with S100a9 acquire apoptotic features. Moreover, we confirm the inhibitory effect of S100a9 on PD-1/PD-L1. Importantly, PD-1/PD-L1 blockade and S100a9 can both activate the PI3K/AKT/mTOR signaling pathway. The cytotoxicity is higher in lower-risk MDS-lymphocytes than in high-risk MDS-lymphocytes, and S100a9 partially rescues the exhausted cytotoxicity in lymphocytes. Our study demonstrates that S100a9 may inhibit MDS-associated tumor escape via PD-1/PD-L1 blockade through PI3K/AKT/mTOR signaling pathway activation. Our findings indicate the possible mechanisms by which anti-PD-1 agents may contribute to the treatment of MDS. These insights may provide mutation-specific treatment as a supplementary therapy for MDS patients with high-risk mutations, such as TP53, N-RAS or other complex mutations.

Objective: To investigate a case of cryptococcal meningoencephalitis (CM) secondary to Sjögren′s syndrome (SS), and to analyze the clinical, pathological features, diagnosis and treatment of the diseases combined with literature review. Methods: Clinical data of 1 case of CM secondary to SS patient were collected, and literatures online were reviewed. Results: The main clinical manifestation consisted of headache, fever and intracranial hypertension. CM was confirmed by cerebrospinal fluid ink stain smear, but the patient still died of complication of amphotericin B treatment. Literature review indicated 9%-18% CM may had a history of autoimmune diseases. Headache because of increased cerebrospinal fluid pressure ocuured in 38%-100%. The efficacy of amphotericin B combined with fluorocytosine in recommended treatment was not satisfactory, and mortality was high (5%-42%). Conclusions: The clinical manifestation of CM secondary to autoimmune diseases is not typical, the abnormal increase of cerebrospinal fluid pressure is its characteristic. The efficacy of treatment is not satisfactory, and the mortality rate is high.

Decitabine and CHG regimen (low-dose cytarabine and homoharringtonine with G-CSF) have been used for treating higher risk myelodysplastic syndrome (MDS). In this study, we retrospectively compared the efficacy and toxicity of the two regimens in 132 MDS patients. Complete remission (CR) was not significantly different between the groups (27.1% with decitabine vs. 30.6% with CHG,p = 0.657). The CR rate with decitabine (58.8%) was significantly higher than that with CHG (7.7%) (p = 0.007) among the patients with poor karyotypes. Five of 23 (21.7%) patients who failed to respond to decitabine achieved CR with CHG, while one of two patients achieved CR with decitabine after failure with CHG. Overall and relapse-free survival were not different between the groups. In conclusion, both decitabine and CHG regimen are effective for higher risk MDS; there is no cross resistance between the regimens. Decitabine might be a better choice for patients with poor karyotypes. [ABSTRACT FROM AUTHOR]

We determined the biological and prognostic significance of five recurrent genetic aberrations in Chinese patients with myelodysplastic syndromes (MDS). A total of 304 Chinese MDS patients were screened for known mutations in five genes ( ASXL1, U2AF1, SF3B1, SRSF2, and EZH2) using next-generation sequencing. Of these, 97 patients (31.9 %) harbored at least one mutation in the five genes, and patients harboring these mutations had distinct clinical features. Incidence ratios for mutations in ASXL1, U2AF1, SF3B1, SRSF2, and EZH2 were 11.8, 8.6, 8.2, 4.3, and 3.6 %, respectively. Patients with U2AF1, SRSF2, and EZH2 mutations more commonly had high-risk than low-risk subtypes, while SF3B1 mutations were frequently confirmed in MDS subtypes with increased ring sideroblasts. Cases with ASXL1 mutations had a higher percentage of complex karyotypes, while U2AF1 mutations were more common in patients with trisomy 8 or 20q deletions. Notably, among 124 patients with a normal karyotype, 48 (38.7 %) had at least one mutation. Patients with U2AF1 or SRSF2 mutations had significantly shorter overall survival (OS) times compared with patients without these mutations ( U2AF1 mutations: median OS, 18 vs 54 months, p = 0.032; SRSF2 mutations: median OS 11 vs 54 months, p = 0.005, respectively). Multivariate analysis showed that the presence of SRSF2 mutations was an independent unfavorable prognostic factor for OS (hazard ratio 2.039; 95 % confidence interval 1.040-4.000; p = 0.038). These data suggest that mutations in epigenetic modification and splicesome genes are common in Chinese patients with MDS, while mutations in U2AF1 and SRSF2 appear to predict an unfavorable prognosis. [ABSTRACT FROM AUTHOR]

To investigate how unselected bone marrow (BM) biopsy examinations could help in the diagnosis of clinically unknown nonhematological tumors. 10,112 plastic-embedded BM biopsy sections were retrospectively analyzed. In the analysis we focused on the following aspects: (1) the frequency of BM involvement arising from clinically unknown nonhematological malignancies, (2) the clinical indication for BM biopsy examination in cases with tumor BM metastasis, (3) the primary sites of the metastatic tumors, and (4) the advantage of plastic-embedded biopsy sections over paraffin-embedded samples and the complementarity of biopsy with aspiration smears. Of the 10,112 BM samples analyzed, 101 (1.0%) were interpreted as being nonhematological tumor metastases. In cases with metastatic tumors, the nonhemocyte-related changes, such as skeletal pain (25%) and bone destruction (5%), were considerably higher than in those without metastasis (3.7 and 0.32%, respectively; P < 0.001). Primary lesions were documented antemortem in 50 of the 101 biopsy-positive cases (49.5%); the most frequent being in the lung, gastric tract, and breast. Using this assay, a higher incidence of metastatic tumors was detected when compared with previously reported paraffin-embedded samples. The frequency of metastatic tumors based on aspiration smears when the positive results for biopsy sections were used as a reference was 74.3%. All the 101 sections with metastatic tumors showed various degrees of myelofibrosis. We concluded that the routine BM biopsy examination is helpful in detecting insidious metastatic nonhematological malignancies. Skeletal pain and bone destruction are critical indications for susceptible patients to undergo BM examination. Plastic embedding of biopsy sections appears to be more sensitive than the paraffin embedding of samples and is an excellent complementation to isolated aspiration smears. [ABSTRACT FROM AUTHOR]

We determined the biological and prognostic significance of five recurrent genetic aberrations in Chinese patients with myelodysplastic syndromes (MDS). A total of 304 Chinese MDS patients were screened for known mutations in five genes (ASXL1, U2AF1, SF3B1, SRSF2, and EZH2) using next-generation sequencing. Of these, 97 patients (31.9 %) harbored at least one mutation in the five genes, and patients harboring these mutations had distinct clinical features. Incidence ratios for mutations in ASXL1, U2AF1, SF3B1, SRSF2, and EZH2 were 11.8, 8.6, 8.2, 4.3, and 3.6 %, respectively. Patients with U2AF1, SRSF2, and EZH2 mutations more commonly had high-risk than low-risk subtypes, while SF3B1 mutations were frequently confirmed in MDS subtypes with increased ring sideroblasts. Cases with ASXL1 mutations had a higher percentage of complex karyotypes, while U2AF1 mutations were more common in patients with trisomy 8 or 20q deletions. Notably, among 124 patients with a normal karyotype, 48 (38.7 %) had at least one mutation. Patients with U2AF1 or SRSF2 mutations had significantly shorter overall survival (OS) times compared with patients without these mutations (U2AF1 mutations: median OS, 18 vs 54 months, p = 0.032; SRSF2 mutations: median OS 11 vs 54 months, p = 0.005, respectively). Multivariate analysis showed that the presence of SRSF2 mutations was an independent unfavorable prognostic factor for OS (hazard ratio 2.039; 95 % confidence interval 1.040-4.000; p = 0.038). These data suggest that mutations in epigenetic modification and splicesome genes are common in Chinese patients with MDS, while mutations in U2AF1 and SRSF2 appear to predict an unfavorable prognosis.

Objective: Compare the characteristics of magnetic resonance imaging（MRI）liver T2*, cardiac T2* and serum ferritin on the assessment of iron overload., Methods: A total of sixty-nine patients from November 2011 to June 2014 were enrolled in this study. Their cardiac and liver iron concentration levels were measured through MRI examination, with other clinical data were collected to perform statistical analysis., Results: The correlation between liver T2* and adjusted serum ferritin（ASF） was statistically significant（P=0.003）. However, no significant correlation was found between cardiac T2* and liver T2*, ASF, respectively. According to the statistical analysis of the 69 cases, it is found that the number of iron overload cases diagnosed by liver T2* was 62 and 20 cases were severe iron overload （32.26%）; the number of iron overload cases diagnosed by ASF was 47 and 14 cases were severe iron overload（29.79%）, while the number of iron overload cases diagnosed by cardiac T2* was only 25 and no severe iron overload cases., Conclusion: Since SF was affected by other factors, it cannot reflect the level of iron overload in human body objectively. Now, liver T2* has become the gold standard for assessment of iron overload because of its good reliability and repeatability. However, cardiac T2* cannot correctly be used as assessment for iron overload, and it is only a method of evaluating the level of cardiac iron deposition.