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Acute myeloid leukemia (AML) is a malignant clonal proliferative disease of immature myeloid cells in hematopoietic system. Although chemotherapy and hematopoietic stem cell transplantation could improve the survival of AML patients, their prognoses are still poor. Previous studies have shown that the abnormal regulation of bone marrow microenvironment (BMM) on leukemia stem cells is one of the important factors that make AML difficult to completely cure and easy to relapse. Studies on AML molecular biology and BMM are increasing. In-depth investigation on the changes of acute leukemia microenvironment and targeted intervention of abnormal BMM are expected to make new breakthroughs in the targeted therapy of AML and to improve the prognosis of patients. This review reviews the progress of BMM and targeted microenvironment therapy in AML.
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Objective:To investigate the significance of Th1/Th2 cytokines in prognostic stratification of acute myeloid leukemia (AML).Methods:A total of 83 patients with newly diagnosed AML from June 2017 to April 2019 in the First People's Hospital of Yunnan Province were collected. According to the Chinese guidelines for diagnosis and treatment of adult acute myeloid leukemia (non-acute promyelocytic leukemia) (2017 edition), AML patients were divided into poor prognosis group (45 cases), moderate prognosis group (19 cases), and good prognosis group (19 cases); moderate prognosis plus poor prognosis was treated as the not good prognosis. Mann-Whitney U test and Kruskal-Wallis H test were used to compare the expression differences of Th1/Th2 cytokines in peripheral blood of different prognosis groups; cytokines with statistical differences among different prognosis groups were selected, and the cut-off value of AML patients with different prognostic stratification distinguished by cytokines was determined by using receiver operating characteristic (ROC) curve. Finally, patients were divided into ≥ cut-off value group and <cut-off value group according to the cut-off value, and then the association of both groups with the prognostic stratification in guideline was also analyzed. Results:The median expression level of tumor necrosis factor (TNF)-β of patients in moderate prognosis group [3.80 pg/ml (2.75 pg/ml, 15.32 pg/ml)] was higher than that of patients in poor prognosis group [2.78 pg/ml (1.28 pg/ml, 3.36 pg/ml)] and good prognosis group [1.61 pg/ml (0.83 pg/ml, 3.04 pg/ml)] ( U=216, P=0.02; U = 312, P < 0.05); the median expression level of TNF-β in good prognosis group was lower than that in poor prognosis group ( U = 562, P = 0.048). There were no statistically significant differences in the expression levels of Th1/Th2 cytokines of AML patients with different prognostic stratification (all P>0.05).The cut-off value of TNF-β was 3.23 pg/ml in good prognosis group and moderate prognosis group, the area under the ROC curve was 0.866 (95% CI 0.753-0.978, P < 0.05); among 26 patients with TNF-β≥ 3.23 pg/ml, 25 (96.2%) patients had not good prognosis. The cut-off value was 3.62 pg/ml for distinguishing between moderate prognosis group and poor prognosis group, the area under the ROC curve was 0.747 (95% CI 0.610-0.884, P = 0.02); 18 (100%) patients with TNF-β≥ 3.62 pg/ml had not good prognosis. The cut-off value was 2.19 pg/ml for distinguishing between good prognosis group and not good prognosis group, the area under the ROC curve was 0.719 (95% CI 0.595-0.842, P = 0.04); among 53 patients with TNF-β≥2.19 pg/ml, 46 (86.8%) patients had not good prognosis. Conclusions:The high expression of TNF-β may indicate that the prognosis of AML patients is not good. When the level of TNF-β was equal or greater than 3.62 pg/ml, it may contribute to the prognostic stratification of AML patients.
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The intestinal flora in patients with leukemia is significantly different from healthy people. Some studies have found that intestinal flora can participate in leukemia progression by regulating the body's immune system and hematopoietic system and affecting the metabolic function, but the underlying molecular mechanism is not clear. Maintaining the intestinal microecological balance and exploring intestinal microbes that can be used as therapeutic targets have a profound significance for prolonging the survival of leukemia patients.
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At present, the treatment methods of lymphoma mainly include the combined chemotherapy, hematopoietic stem cell transplantation, immunotherapy and new targeted therapies, but the treatment-related drug resistance, recurrence, extranodal and central nervous system infiltration, and leukemia transformation are still intractable problems that need to be solved in clinical practice. Studies have shown that cytokines are expressed to varying degrees in patients with lymphoma, which are significantly related to the progression of lymphoma, poor prognosis, chemotherapy response, and drug resistance. It has been confirmed that interleukin 6 (IL-6) and IL-10 are highly expressed in all types of lymphoma, and IL-10 is highly expressed in the cerebrospinal fluid of central nervous system lymphoma, all of which indicate a poor prognosis. This article reviews the role of cytokines in the development, treatment and prognosis of lymphoma.
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Objective:To investigate the expression of macrophage migration inhibitory factor (MIF) in bone marrow fluid and peripheral blood of patients with acute myeloid leukemia (AML) and its effect on the expression of interleukin-8 (IL-8) in bone marrow mesenchymal stem cells (BM-MSC).Methods:Fifty bone marrow fluid samples and 50 peripheral blood samples were collected from 50 patients with AML diagnosed in the First People's Hospital of Yunnan Province from October 2017 to January 2019, of which 17 patients were newly diagnosed, 26 patients were complete remission (CR), and 7 patients were partial remission (PR) or non-remission (NR). Fifty plasma samples from 50 healthy subjects and 50 bone marrow fluid samples from 50 patients with iron deficiency anemia were used as the controls. Enzyme-linked immunosorbent assay (ELISA) was used to detect the level of MIF protein in the samples, and the relationship between MIF expression level and clinicopathological characteristics of AML patients was analyzed. BM-MSC was successfully isolated and cultured from 42 bone marrow fluid samples of AML patients, the suitable samples for experiment were chosen and divided into BM-MSC control group (untreated BM-MSC), recombinant human macrophage migration inhibitory factor (rhMIF) group and rhMIF+ISO-1 group. ELISA and real-time fluorescence quantitative polymerase chain reaction were used to detect the expression level of IL-8 protein and mRNA in each BM-MSC group.Results:The expression levels of MIF protein in bone marrow fluid and plasma in AML group were (24.9±7.7) ng/ml and (60.5±12.1) ng/ml, the difference was statistically significant ( P < 0.01), and those in control group were (5.3±2.6) ng/ml and (2.0±1.1) ng/ml, respectively, and there were statistical differences between the two groups (t values were 136.71, 33.97 and 17.58, all P < 0.01). MIF protein expression levels in bone marrow fluid and plasma of AML patients in newly diagnosed group and PR+NR group were higher than those in CR group, and the differences were statistically significant (all P < 0.01). MIF protein expression levels were higher in bone marrow fluid and plasma of patients with ≥60 years of age, peripheral blood white blood cell count ≥30×10 9/L and bone marrow myeloblast ratio > 0.50 (all P < 0.05), but the differences were not statistically significant between patients with different gender (both P > 0.05). The detection results of each BM-MSC group showed that rhMIF promoted the IL-8 expression in BM-MSC at the gene and protein levels, which could be inhibited by the MIF inhibitor ISO-1 (all P < 0.01). Conclusion:The increased expression levels of MIF in bone marrow fluid and plasma of patients with AML are associated with the disease progression, and rhMIF can promote the expression of IL-8 in BM-MSC.
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Objective@#To investigate the current status and real performance of the detection of RUNX1-RUNX1T1 fusion transcript levels and WT1 transcript levels in China through interlaboratory comparison.@*Methods@#Peking University People’s Hospital (PKUPH) prepared the samples for comparison. That is, the fresh RUNX1-RUNX1T1 positive (+) bone morrow nucleated cells were serially diluted with RUNX1-RUNX1T1 negative (-) nucleated cells from different patients. Totally 23 sets with 14 different samples per set were prepared. TRIzol reagent was added in each tube and thoroughly mixed with cells for homogenization. Each laboratory simultaneously tested RUNX1-RUNX1T1 and WT1 transcript levels of one set of samples by real-time quantitative PCR method. All transcript levels were reported as the percentage of RUNX1-RUNX1T1 or WT1 transcript copies/ABL copies. Spearman correlation coefficient between the reported transcript levels of each participated laboratory and those of PKUPH was calculated.@*Results@#①RUNX1-RUNX1T1 comparison: 9 samples were (+) and 5 were (-) , the false negative and positive rates of the 20 participated laboratories were 0 (0/180) and 5% (5/100) , respectively. The reported transcript levels of all 9 positive samples were different among laboratories. The median reported transcript levels of 9 positive samples were from 0.060% to 176.7%, which covered 3.5-log. The ratios of each sample’s highest to the lowest reported transcript levels were from 5.5 to 12.3 (one result which obviously deviated from other laboratories’ results was not included) , 85% (17/20) of the laboratories had correlation coefficient ≥0.98. ②WT1 comparison: The median reported transcript levels of all 14 samples were from 0.17% to 67.6%, which covered 2.6-log. The ratios of each sample’s highest to the lowest reported transcript levels were from 5.3-13.7, 62% (13/21) of the laboratories had correlation coefficient ≥0.98. ③ The relative relationship of the reported RUNX1-RUNX1T1 transcript levels between the participants and PKUPH was not always consistent with that of WT1 transcript levels. Both RUNX1-RUNX1T1 and WT1 transcript levels from 2 and 7 laboratories were individually lower than and higher than those of PKUPH, whereas for the rest 11 laboratories, one transcript level was higher than and the other was lower than that of PKUPH.@*Conclusion@#The reported RUNX1-RUNX1T1 and WT1 transcript levels were different among laboratories for the same sample. Most of the participated laboratories reported highly consistent result with that of PKUPH. The relationship between laboratories of the different transcript levels may not be the same.
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[ ABSTRACT] Tyrosine kinase inhibitors ( TKIs) are now advocated as the first-line treatment for chronic myeloid leukemia ( CML) , but facing resistance and relapse .Leukemia stem cells ( LSCs ) are leukemia-initiating cells as the source of resistance and relapse .It is therefore important to discover the molecular biomarker of LSCs for developing anti -LSC strategies in leukemic therapy .15-Lipoxygenase (15-LO) is a key enzyme in the pathway of arachidonic acid and plays an important role in the occurrence and development of CML , which is specifically required for chronic myeloid LSCs . This review summarizes the influence of 15-LO on the chronic myeloid LSC characteristics of marked survival , self-renewal, proliferation , differentiation and apoptosis .
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Objective To investigate the inhibitory effect of rhIFN-γ on human chronic myeloid leukemia cell line K562,and the impaction on the expression of CD123.Methods MTT method was used to test cell relative viability with rhIFN-γ at different concentrations.The expression of CD123 on K562 ceils was detected by flow cytometry.Results The relative inhibition of K562 cells proliferation was hampered when the cells were treated with rhIFN-γ for 72 h at the concentration of 5 x 10P ～ 108 U/L,respectively.However,rhIFN-γ at 2 x 105 U/L was benefit to K562 cells proliferation.After treatment with rhIFN-γ at 0,2 x 105 U/L and 107 U/L,the percentages of CD123 expression on K562 cells were (4.10 ± 1.46) ％,(7.2 ± 2.50) ％ as well as (21.6 ± 1.17) ％,respectively.Compared with the control group,107 U/L rhIFN-γ significantly increased the expression of CD123 on K562 cells (P＜0.05).Conclusion The effect of rhIFN-γ on the growth of K562 cells has two aspects (inhibition or proliferation),and it can increase the expression of CD 123.
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Pinellia ternata in traditional Chinese medicinal herbs,planted and wide application range,with great development value.Medicinal components of pinellia ternata have obviously anti-tumor effect.In this paper,the author summarized the research result of anti-tumor effect of medicinal components of pinellia ternata,sought for a proven foundation of anti-tumor mechanism of medical components of pinellia ternata.
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BACKGROUND: Uncontrolled-rate freezing in -80 ℃ refrigerator is convenient, while controlled-rate freezing in -196 ℃ liquid nitrogen is reliable and long-term, the combination of the two can simplify the process and has been successfully used in clinics. OBJECTIVE: To explore the influences of different cryoprotectants by ladder-style freezing from -80 ℃ low temperature refrigerator to liquid nitrogen on the cryopreservation of hemopoietic stem cells. METHODS: The experiments were divided into four groups: 10% dimethyl sulfoxide (DMSO) group, 5% DMSO combined with 3% hydroxyethyl starch group, 5% DMSO combined with 0.25 mol/L trehalose group, 5% DMSO combined with 3% hydroxyethyl starch and 0.25 mol/L trehalose group. Peripheral hemopoietic stem cells were cryopreserved by ladder-style freezing from -80 ℃ low temperature refrigerator to liquid nitrogen. The ultrastructural changes were examined by transmission electron microscopy, the expressions of Annexin-V, PI and Caspase-3 were detected by flow cytometry. RESULTS AND CONCLUSION: There was no significant difference in survival rate, apoptotic rate and necrotic rates of the cryopreserved cells in the four groups (P > 0.05). The ultrastructural changes had no significant difference under the transmission electron microscopy. The viability was more than 90% in frozen-thawed mononuclear cell colonies, and the apoptosis was roughly 50% in the frozen-thawed CD45+ cell population, which contained many mature cells. Of hemopoietic stem cells, early stage cells have greater resistance to damage of cryopreservation than late stage cells. It is concluded that the addition of hydroxyethyl starch or trehalose into DMSO exhibits no synergistic protective effect on the cryopreservation of hemopoietic stem cells.
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Objective To explore the influence of cryopreservation by ladder-style freezing from low temperature refrigerator to liquid nitrogen on hemopoietic stem cell(HSC)transplantation.Methods From April 2001 to April 2006,31 cases treated with HSC transplantation were randomized to controlled-rate freezer-liquid nitrogen group(n=15)and refrigerator-liquid nitrogen group(n=16)in Department of Hematology of 1st People's Hospital of Yunnan Province.The hemopoietic reconstitution time was observed,and the viability of HSC was determined by trypan blue exclusion test in two groups.Results No significant differences were found in transfusion values of mononuclear cells(MNC)and CD34+ cells,rates of trypan blue exclusion and time of ANC0.05).Conclusion Cryopreservation of HSC can produce successful engraftment by ladder-style freezing which has cryoprotectant solution containing final concentrations of 3-percent hydroxyethyl starch,4-percent human serum albumin,and 5-percent DMSO,and its effect is the same as traditional controlled-rate method with 10-percent DMSO cryoprotectant.The new freezing procedure is faster and easier,and freezing cost is reduced.