[Research Progress of m6A Demethylase FTO and Its Inhibitors in Acute Myeloid Leukemia --Review].

Obesity-associated protein (FTO) is an important m6A demethylase that regulates RNA methylation modification and can promote the proliferation of acute myeloid leukemia(AML) cells. FTO regulates the methylation level of AML through multiple cellular signaling pathways such as FTO/RARA/ASB2, FTO/m6A/CEBPA, and PDGFRB/ERK, and participates in the occurrence, development, treatment and prognosis of AML. At present, studies have found that a variety of inhibitors targeting FTO have shown good anti-leukemia effects, and the study of FTO will provide new ideas for the treatment of AML. This review focus on the mechanism of action of FTO in AML and the research progress of FTO inhibitors in AML.

Immune Status and Chemokine C Receptor 7 Expression in Primary in Patients with Immune Thrombocytopenia

Objective: The present study investigated immune disorders and chemokine C receptor 7 (CCR7) expression in primary immune thrombocytopenia (ITP) patients and analyzed their changes and clinical significance before and after treatments. Materials and Methods: Flow cytometry was used to detect the proportion of different immune cell subsets in the peripheral blood of 42 patients with ITP and 20 healthy controls at different time points. Treatments included first-line drugs, such as glucocorticoids and intravenous immunoglobulin, and second-line therapy, such as interleukin-11 and thrombopoietin receptor agonists. Results: An elevated CD4/CD8 ratio and decreased natural killer (NK) cells and CD4+CD25+CD127low regulatory T-cells (Tregs) were found in pretreatment ITP patients compared to healthy controls. The newly diagnosed group had a higher CD4/CD8 ratio and more NK cells than the relapsed group. Treg levels of the remission group were higher than those of the recurrence group. The CD4+CCR7+, CD8+CCR7+, and CCR7+ subsets of B cells and NK cells showed higher increases in the newly diagnosed and relapsed group compared to controls and the remission group. The values for the CD4+CCR7+ and CD8+CCR7+ subsets in the relapsed group were slightly higher than those in the newly diagnosed group. The CCR7+ subsets of CD4+ T-cells, CD8+ T-cells, NK cells, and B cells had lower values in the remission group compared to the relapsed group. Higher levels of the CD8+CCR7+ subset and lower levels of NK cells were found in the remission group compared to the controls. The ratio between the CD4+CCR7+ subset and CD8+CCR7+ subset was lower in ITP patients than in healthy controls. There was a negative correlation between the CD8+CCR7+ subset and platelet count in the ITP patients. Conclusion: ITP patients with CCR7 had immune disorders and high heterogeneity, and CCR7 was found to be involved in the pathogenesis of ITP. Further studies are needed to investigate effective treatments for ITP by targeted regulation of CCR7.

Early Death and Survival of Patients With Acute Promyelocytic Leukemia in ATRA Plus Arsenic Era: A Population-Based Study.

Most randomized trials for acute promyelocytic leukemia (APL) have investigated highly selected patients under idealized conditions, and the findings need to be validated in the real world. We conducted a population-based study of all APL patients in Zhejiang Province, China, with a total population of 82 million people, to assess the generalization of all-trans retinoic acid (ATRA) and arsenic as front-line treatment. The outcomes of APL patients were also analyzed. Between January 2015 and December 2019, 1,233 eligible patients were included in the final analysis. The rate of ATRA and arsenic as front-line treatment increased steadily from 66.2% in 2015 to 83.3% in 2019, with no difference among the size of the center (≥5 or <5 patients per year, p = 0.12) or age (≥60 or <60 years, p = 0.35). The early death (ED) rate, defined as death within 30 days after diagnosis, was 8.2%, and the 3-year overall survival (OS) was 87.9% in the whole patient population. Age (≥60 years) and white blood cell count (>10 × 109/L) were independent risk factors for ED and OS in the multivariate analysis. This population-based study showed that ATRA and arsenic as front-line treatment are widely used under real-world conditions and yield a low ED rate and a high survival rate, which mimic the results from clinical trials, thereby supporting the wider application of APL guidelines in the future.

Associations between genetic polymorphisms in interleukin-10 and hematological oncology: evidence from a meta-analysis.

Background: Associations between polymorphisms in interleukin-10 (IL-10) and hematological oncology were already explored by many genetic association studies, with controversial findings. The aim of this meta-analysis was to more comprehensively analyze associations between polymorphisms in IL-10 and hematological oncology by combing the results of all relevant studies.Methods: Eligible articles were searched from Pubmed, Embase, WOS and CNKI. The latest literature searching update was performed on 8 October 2019. We used Review Manager to combine the results of eligible studies.Results: Forty-one articles were included in this meta-analysis. IL-10 rs1800890 polymorphism was found to be significantly associated with hematological oncology under AA vs. TT+TA (recessive comparison, OR = 1.12, 95% CI 1.02-1.24), and rs1800896 polymorphism was also found to be significantly associated with hematological oncology under AA vs. AG+GG (dominant comparison, OR = 0.89, 95% CI 0.83-0.95) in overall combined analyses. In subgroup analyses, we observed positive results for rs1800871 (recessive comparison), rs1800872 (dominant, recessive and allele comparisons), and rs1800896 (dominant and allele comparisons) polymorphisms in the non-Hodgkin's lymphoma (NHL) subgroup. Besides, we also detected positive associations between rs1800872 polymorphism and acute leukemia (AL) (dominant and recessive comparisons) and found significant associations between rs1800896 polymorphism and chronic leukemia (CL) (recessive comparison).Conclusion: In summary, this meta-analysis demonstrated that IL-10 rs1800890, rs1800896, rs1800871 and rs1800872 polymorphisms may confer susceptibility to hematology oncology, especially for NHL.

Role of Th 1- and Th 2- Chemokine Receptor in the Diagnosis and Prognosis of Primary Immune Thrombocytopenia.

BACKGROUND: The diagnostic and prognostic role of Th-1 chemokine receptor and Th-2 chemokine receptor in patients with primary immune thrombocytopenia has not been investigated extensively so far. In this study, our goal is to explore the diagnostic and prognostic role of C-C chemokine receptor 3 (CCR3) and C-C chemokine receptor 5 (CCR5) in patients with primary immune thrombocytopenia. METHODS: The expression levels of CCR3 and CCR5 were measured in peripheral blood mononuclear cells of pa-tients with primary immune thrombocytopenia and healthy subjects. The relationship between the expression levels of CCR3 and CCR5 and clinicopathological characteristics was analyzed. The diagnostic accuracy of CCR3 and CCR5 as biomarkers to discriminate primary immune thrombocytopenia patients from healthy subjects was determined. Univariate and multivariate Cox regression analysis were performed to determine the prognosis value of CCR3 and CCR5 in primary immune thrombocytopenia. The outcome of primary immune thrombocytopenia patients was also evaluated. RESULTS: Compared to healthy subjects, the expression level of CCR3 was significantly downregulated and CCR5 was significantly upregulated (p < 0.05). The expression levels of CCR3 and CCR5 were significantly correlated with bleeding times and platelet counts at diagnosis (p < 0.05). CCR3 and CCR5 could act as a suitable biomarker for differentiating the primary immune thrombocytopenia patients from healthy subjects. CCR3 and CCR5 were independent prognostic factors. Overexpression of CCR5 and low expression of CCR3 lead to poor clinical benefits and indicated poor prognosis of primary immune thrombocytopenia. CONCLUSIONS: To summarize, our results suggested that CCR3 and CCR5 could act as suitable biomarkers and indicated poor prognosis of primary immune thrombocytopenia.

[Clinical Significance of the Balanceshift of Th1 and Th2 Type Cytokines in Patients with Primary Immune Thrombocytopenic Purpura Detected by Cytometric Bead Array].

OBJECTIVE: To investigate the levels of Th1/Th2 cytokines in peripheral blood of patients with primary immune thrombocytopenic purpura(ITP) before and after treatment and their clinical significance. METHODS: Ninety-eight cases of ITP were treated with glucocorticoid(GC), then were divided into 2 groups: effectively treated group and uneffectively treated group according to efficacy of treatment, 40 healthy persons confirmed by health examination were selected and enrolled in control group. The levels of Th1 cytokines(IFN-γ,TNFα,IL-2) and Th2 cytokines(IL-4,IL-5,IL-10) were detected by cytometric bead array before and at 4 weeks, 3 and 6 months after treatment and the relationship among detected indexes was analyzed. RESULTS: Before treatment with glucocorticoid, the levels of Th1 type cytokines were in 98 patients with ITP were higher and the levels of Th2 type cytokines were lower, compared with the healthy controls(P<0.05). The IL-2/IL-4 ratio was significantly higher than that of healthy controls(P<0.05). After treatment, the levels of Th1 type cytokines in effectively treated group were significantly decreased and the levels of Th2 type cytokines were significantly increased, compared with level before treatment(P<0.05). The IL-2/IL-4 ratio was significantly decreased after treatment for 6 months, compared with that before treatment(1.05±0.43 vs 2.53±0.72)(P<0.05), but the level of Th1 or Th2 type cytokines did not obviously changed. CONCLUSION: Peripheral blood Th1 and Th2 cells express abnormally in ITP patients, ITP is a Th1 dominated disease; the change of IL-2/IL-4 ratio before and after treatment correlated with the prognosis of ITP patients, displaying clinical significance for ITP individual therapy.

[Bioavailability of dissolved organic nitrogen components in the lake sediment to alage].

Samples in the sediments of Wuliangsuhai and Erhai Lake were selected, and the technologies of XAD-8 resins separation and three dimensional fluorescence excitation-emission matrix (3DEEM) spectra were applied, in order to study the bioavailability of dissolved organic nitrogen components to alage under the room cultivation. The obtained results showed that: (1) Average loss of DON and DOC from sediments was below 5% after dividing DON into different groups, which means the technology of XAD- 8 resins separation could be used in the study of DON components in the lake sediment. (2) Through 3DEEM analysis, hydrophilic and hydrophobic DON was dominated by protein-like and humic-like materials in the lake sediment, respectively. (3) Under the hydrophilic component condition, growth curves of algae tended to show an "S" shape with a straight upward trend in the sediments of Wuliangsuhai and Erhai lake,with the maximum algal density reaching 535.5 x 10(4) and 709.5 x 10(4) per milliliter, respectively. Meanwhile, the DON concentrations were significantly reduced after cultivation to 2.46 and 2.98 mg x L(-1), respectively, which suggests that hydrophilic DON in the lake sediment was the bioavailable organic nitrogen for alage. (4) Under the hydrophbic component conditions, growth curves of algae tended to show a "unimodal" shape in the sediments of Wuliangsuhai and Erhai lake,with the maximum algal density reaching 113.5 x 10(4) and 275.5 x 10(4) per milliliter,respectively. The DON concentrations were significantly reduced during the early cultivation period, and then kept stable in the late period, which suggests that the hydrophobic DON component bioavailable to alage was low in short-term, and the hydrophobic DON component had hardly any positive effect on the growth of algae.

[Fas-FasL and caspase-3 signal transduction pathway and apoptosis of peripheral T lymphocytes in ITP patients].

OBJECTIVE: To explore the relationship between Fas-FasL-mediated signal transduction pathway and apoptosis of T lymphocyte subset in ITP patients. METHODS: The expression rates of membrane Fas, FasL and intracellular activated caspase-3 in peripheral T lymphocyte subset were determined by flow cytometry. T cell subsets with caspase-3 protein expression were detected by Western blot. RESULTS: As compared with that in healthy control group [(29.4 +/- 8.2)%], the expression rate of membrane Fas on CD4+ T cells was significantly increased in ITP patients [(42.1 +/- 9.5)%] (P < 0.05), however, that on CD8+ T cells was only slightly increased [(9.3 +/- 6.0)% vs (13.4 +/- 5.8)%] with no statistical significance (P > 0.05). The expression rate of FasL on T cell subset in ITP patients was significantly increased (P < 0.05), and that of intracellular activated caspase-3 in T cell subset in ITP patients was notably higher than that in healthy control group (P < 0.05). Western blot analysis showed that the expression of pro-caspase-3 and cleaved-caspase-3 in CD4+ T cells in patients with ITP after treatment were significantly reduced compared with those before treatment (P < 0.05). CONCLUSION: Apoptosis of T lymphocyte subset in ITP patients is accelerated. It is possible that Fas-FasL signal transduction pathway plays an important role in the induction of the apoptosis. The degree of apoptosis of T lymphocytes closely correlates with the disease's activity in ITP patients. Hormone therapy may interfere with Fas-FasL signal transduction pathway of apoptosis.

[Significance of detecting platelet associated antibody and platelet membrane glycoprotein for diagnosis of immune thrombocytopenia].

The aim of this study was to explore application value of detecting platelet associated antibody and platelet membrane glycoprotein in the diagnosis and prognosis for immune thrombocytopenia. The platelet associated immunoglobulin (PAIg) and platelet membrane glycoprotein (CD41, CD61, GPIIb/IIIa) in 76 cases of immune thrombocytopenia and 30 healthy subjects were determined by FCM. The results showed that PAIg level in ITP patients included PAIgG (31.25 +/- 18.06)%, PAIgM (32.41 +/- 15.51)%, PAIgA (23.39 +/- 16.67)% which were remarkedly higher than in health control (10.48 +/- 5.05)%, (9.40 +/- 4.42)% and (7.23 +/- 3.61)% (P < 0.001). In patients with secondary immune thrombocytopenia (chronic aplastic anemia, SLE, Evans syndrome, liver cirrhosis hypersplenism, etc), PAIg level was higher than that in control group, while the platelet membrane glycoprotein in the blood of these patients was lower than that in control group. The level of PAIg decreased (P < 0.05) after treatment, but platelet membrane glycoprotein increased (P < 0.01). The result suggested that measurements for platelet membrane glycoprotein and platelet associated antibody by FCM were practical with high sensitivity, rapidity and simplicity used as a routine method in diagnosis and evaluation of the therapeutic effects in immune thrombocytopenia patients.