Cytokine levels in patients with non-M3 myeloid leukemia are key indicators of how well the disease responds to chemotherapy.

Acute myeloid leukemia (AML) is a malignant hematological neoplastic disease. Autocrine or paracrine cytokines released by leukemic cells regulate the proliferation of AML cells. It is uncertain whether cytokines can indicate whether patients with AML are in remission with chemotherapy. The goal of this study was to evaluate the levels of Th1/Th2/Th17 cytokines in AML patients before and after chemotherapy to determine whether the cytokine levels could predict disease remission after chemotherapy. It was found that the levels of IL-5, IL-6, IL-8, IL-10, TNF-α, TNF-ß, IL-17F, and IL-22 were significantly increased at the time of AML diagnosis in patients who achieved remission after two chemotherapy treatments (P < 0.05). After chemotherapy, the cytokine levels were reduced in patients with remission, while the levels of IL-6 and IL-8 were raised in patients without remission (P < 0.05). A comparison of cytokine levels before and after chemotherapy in patients who achieved remission showed areas under the curve (AUCs) of 0.69 for both IL-6 and IL-8. In addition, a comparison of the remission and non-remission groups after chemotherapy showed an AUC of 0.77 for IL-6. We then calculated the cutoff value using receiver operating characteristic curves. Values of IL-6 < 9.99 and IL-8 < 8.46 at the time of diagnosis were predictive of chemotherapy success and remission, while IL-6 > 14.89 at diagnosis suggested that chemotherapy would not be successful and remission would not be achieved. Multifactorial analysis showed that age, Neu, IL-6, and IL-8 were independent risk factors for AML prognosis, and IL-6 (OR = 5.48, P = 0.0038) was superior to age (OR = 3.36, P = 0.0379), Neu (OR = 0.28, P = 0.0308), IL-8 (OR = 0.0421, P = 0.0421). In conclusion, IL-6 levels were found to be predictive of the likelihood of remission.

[The Latest Research Progress of Mesenchymal Stem Cells Derived from Multiple Myeloma Patients --Review].

Multiple myeloma (MM) is a malignant proliferative disease of plasma cells. Bone marrow mesenchymal stem cells (MSC) play an important role in the progression of MM. Compared with normal donor derived MSC (ND-MSC), MM patients derived MSC (MM-MSC) exhibit abnormalities in genes, signaling pathways, protein expression levels and cytokines secreted by themselves. Moreover, the exosomes of MM-MSC can interact with the bone marrow microenvironment. The above reasons can lead to MM cell proliferation, chemoresistance, impaired osteogenic differentiation of MM-MSC, and affect the immunomodulatory capacity of MM patients. In order to further understand the pathogenesis and related influencing factors of MM, this paper reviews the latest research progress of MM-MSC.

[The Latest Research Progress on Myelodysplastic Syndrome Patient-derived Mesenchymal Stem Cell--Review].

Myelodysplastic syndrome (MDS) are a heterogeneous group of hematological malignancies. Currently, in addition to demethylated chemotherapy and hematopoietic stem cell transplantation, MDS patient-derived mesenchymal stem cells (MDS-MSC) play an important role in understanding the pathogenesis of MDS and related therapeutic targets. For example, abnormal expression of DICER1 gene, abnormalities of PI3K/AKT and Wnt/ß-catenin signaling pathways provide new therapeutic targets for MDS. In addition, MDS-MSC is also affected by abnormal microenvironment of the body, such as inflammatory factor S100A9, as well as hypercoagulation and iron overload. In this review, genes, signaling pathways, cytokines, hematopoietic microenvironment, and the effect of therapeutic drugs for MDS-MSC were briefly summarized.

Increased Cytokine Levels Assist in the Diagnosis of Respiratory Bacterial Infections or Concurrent Bacteremia in Patients With Non-Hodgkin's Lymphoma.

Non-Hodgkin's lymphoma (NHL) is a form of tumor that originates in the lymphoid tissues. Bacterial infections are very common in NHL patients. Because most of the patients do not experience apparent symptoms during the initial stage of infection, it is difficult to detect the underlying condition before it progresses to a more critical level. The activation of the cytokines is a hallmark of inflammation. Due to the advantages of short detection time and high sensitivity of cytokines, many studies have focused on relationship between cytokines and infection. However, few studies have been conducted on NHL patients with infection. Therefore, we reviewed the cytokine profiles of 229 newly diagnosed NHL patients and 40 healthy adults to predict respiratory bacterial infection and bacteremia. Our findings revealed that IL-6(41.67 vs 9.50 pg/mL), IL-8(15.55 vs 6.61 pg/mL), IL-10(8.02 vs 4.52 pg/mL),TNF-ß(3.82 vs 2.96 pg/mL), IFN- γ(4.76 vs 2.96 pg/mL), body temperature(37.6 vs 36.5°C), CRP(20.80 vs 4.37 mg/L), and PCT(0.10 vs 0.04 ng/mL) levels were considerably greater in NHL cases with respiratory bacterial infections relative to NHL cases without infection (P<0.05). Furthermore, IL-6(145.00 vs 41.67 pg/mL), IL-8(34.60 vs 15.55 pg/mL),temperature(38.4 vs 37.6°C), PCT(0.79 vs 0.10 ng/mL), and CRP(93.70 vs 20.80 mg/L) levels in respiratory infectious NHL patients with more severe bacteremia were considerably elevated than in patients with respiratory bacterial infections only (P<0.05). Remarkably, increased levels of IL-6 and IL-8 are effective in determining whether or not pulmonary bacterial infectious NHL patients have bacteremia. Temperature, PCT, and CRP all have lower sensitivity and specificity than IL-6. IL-6 ≥18.79pg/mL indicates the presence of pulmonary bacterial infection in newly diagnosed NHL patients, and IL-6 ≥102.6pg/mL may suggest pulmonary bacterial infection with bacteremia. In short, this study shows that cytokines can be advantageous in the diagnosis and differentiation of pulmonary bacterial infection and bacteremia in newly diagnosed NHL patients and may also guide for the use of clinical antibiotics.

Complement 4 Aids in the Prediction of Newly Diagnosed Multiple Myeloma Outcome in Patients.

BACKGROUND: A cure for the heterogeneous hematological malignancy multiple myeloma (MM) is yet to be developed. To date, the early risk factors associated with poor outcomes in MM have not been fully elucidated. Studies have shown an aberrant complement system in patients with MM, but the precise association necessitates elucidation. Therefore, this study scrutinizes the correlation between serum complement level and the disease outcome of patients with MM. METHODS: A retrospective analysis of 72 patients with MM (new diagnosis) with complement C4 and C3 along with common laboratory indicators was done. The Pearson χ2 test and the Mann-Whitney U-test were done to evaluate categorical or binary variables and intergroup variance, respectively. Kaplan-Meier test and Cox proportional hazards regression were used for quantification of overall survival (OS) and univariate or multivariate analyses, respectively. RESULTS: The Cox proportional hazard model analysis unveiled the following: platelet ⩽115.5 × 109/L (hazard ratio [HR] = 5.82, 95% confidence interval [CI] = 2.522-13.436, P < .001), complement C4 ⩽0.095 g/L(HR = 3.642, 95% CI = 1.486-8.924, P = .005), age ⩾67 years (HR = 0.191, 95% CI = 0.078-0.47, P < .001), and bone marrow plasma cell percentage ⩾30.75% (HR = 0.171, 95% CI = 0.06-0.482, P = .001) can be used as independent predictors of OS. Of these, advanced age, low platelet level, and a high proportion of bone marrow plasma cells have been implicated in poor outcomes in patients with MM. Interestingly, a low complement 4 level can function as a new indicator of poor prognosis in patients with MM. CONCLUSION: Low levels of C4 are indicative of a poor outcome in newly diagnosed patients with MM.

A novel study on the immunomodulatory effect of umbilical cord derived mesenchymal stem cells pretreated with traditional Chinese medicine Asarinin.

Allogeneic hematopoietic stem cell transplantation (HSCT) remains the key for the treatment of malignant hematological diseases, and acute graft-versus-host disease (aGVHD) that might occur after allogenic transplantation can be life threatening and promote disease recurrence. GVHD damages the various parts of the body by upregulating T helper 1 cytokines (Th1) cytokines and stimulating CD4、CD8 + T cells. GVHD can exhibit significant immunoregulatory effects, but could be easily affected by the mesenchymal stem cells (MSC) environment, and hence the MSC immunosuppressive effects on GVHD remain unpredictable. Hence, to better understand the role of MSC in the prevention and treatment of GVHD, umbilical cord derived mesenchymal stem cells (UC-MSC) were pre-treated with Chinese medicine Asarinin and IFN-γ. In the mix lymphocyte reaction, we found that Asarinin pre-treated UC-MSC can exert significantly greater inhibition towards the proliferation of CD4 and CD8 + T cells, down-regulate Th1 type cytokines, up-regulate Th2 type cytokines, and reduce the inflammatory damage to liver, lung and intestine of aGVHD mice model. Moreover, Asarinin can cooperate with IFN-γto promote UC-MSC to secrete indoleamine 2,3-dioxygenase (IDO). Our findings establish that Asarinin pre-treated UC-MSC can significantly promote the immunosuppressive effects of MSC on aGVHD after hematopoietic stem cell transplantation.