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Objective:To investigate the expression level of small nucleolar RNA SNORD15A in bone marrow of patients with acute leukemia (AL) and its relationship with clinical characteristics and prognosis of patients.Methods:Bone marrow blood samples of 53 newly treated AL patients and 29 healthy subjects without clinical diagnosis of hematologic diseases or other malignant diseases (control group) at the Affiliated Hospital of Guangdong Medical University from March 2018 to December 2021 were collected. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the relative expression of SNORD15A in bone marrow blood mononuclear cells of the two groups. The median relative expression of SNORD15A (0.148) was used as the boundary, and AL patients were divided into low expression group (<0.148) and high expression group (≥0.148). The relationship between the expression level of SNORD15A and the clinical characteristics, clinical indicators and overall survival (OS) of AL patients was analyzed. Kaplan-Meier method was used for survival analysis and log-rank test was performed; Cox proportional hazards model was used for univariate and multivariate analyses of OS of patients.Results:The relative expression of SNORD15A was 0.148 (0.012-1.376) in newly treated AL patients and 0.921 (0.513-2.288) in the control group, and the difference was statistically significant ( Z = -6.85, P < 0.01). The differences in SNORD15A relative expression between patients with different prognostic stratification, efficacy and with or without fever and bleeding were statistically significant (all P < 0.05). The differences in platelet count, plateletcrit and albumin levels between SNORD15A low expression group and high expression group were statistically significant (all P < 0.05), and the differences in molecular biology and cytogenetic characteristics were not statistically significant (all P > 0.05). The patients in SNORD15A high expression group had better OS than the low expression group ( P < 0.05). The results of univariate Cox regression analysis showed that SNORD15A was an influencing factor for patients' OS ( HR = 0.063, 95% CI 0.005-0.766, P < 0.05); the results of multivariate Cox regression analysis showed that fatigue ( HR = 4.754, 95% CI 1.014-22.290), fever ( HR = 0.147, 95% CI 0.029-0.746) and hemoglobin ( HR = 0.970, 95% CI 0.944 -0.998) were independent influencing factors for OS (all P < 0.05). Conclusions:SNORD15A is lowly expressed in AL and may be an indicator for disease monitoring and prognostic assessment in AL patients.
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Minimal residual disease (MRD) has been used not only for relapse prediction, prognosis re-classification and directing pre-emptive therapy of patients with acute leukemia, but also in the field of therapy for patients with other hematological malignancies or solid tumors. A deep understanding of the intension and extension of MRD is important for exploring novel methods for accurate prediction of relapse and consummating the individualized intervention strategies for malignant tumors.
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Objective:To investigate the clinical characteristics, diagnosis, treatment and prognosis of acute leukemia (AL) with NUP98-DDX10 fusion gene-positive.Methods:The clinical data of 2 AL patients with NUP98-DDX10 fusion gene-positive who admitted to Blood Diseases Hospital, Chinese Academy of Medical Sciences in April 2020 and February 2021, respectively were retrospectively analyzed. Transcriptome gene sequencing was used to detect fusion gene, and the fusion gene fragment was amplified by using reverse transcription polymerase chain reaction (RT-PCR), and Sanger sequencing was used to clarify sequences. The clinical and experimental indicators characteristics were analyzed and the relevant literatures were reviewed.Results:According to the clinical diagnosis, 1 patient was diagnosed as acute myeloid leukemia M 5 (AML-M 5) and 1 patient was diagnosed as acute leukemia of ambiguous lineage, not otherwise specified (ALAL-NOS). The AML-M 5 patient presented with severe coagulation abnormalities, and fulfilled the diagnostic criteria for diffuse intravascular coagulation (DIC) at the initial visit. Transcriptome sequencing of 2 patients showed NUP98-DDX10 fusion gene- positive. RT-PCR confirmed that sequencing results identified 2 different splice fusion modes: one was NUP98 exon 14 fused with DDX10 exon 7(usually called "type Ⅱ"), the other was NUP98 exon 14 fused with DDX10 exon 13, which was never reported and named as "type Ⅳ". From 1997 to 2018, a total of 16 cases with NUP98-DDX10 related hematologic neoplasms were reported in the literature. A summary analysis of 16 cases added with 2 patients in our center included 13 males and 5 females with median age 31.5 years (0.08-61 years). The median overall survival was 12 months (1-46 months). Conclusions:A novel fusion gene NUP98-DDX10 transcriptome is identified in ALAL-NOS patient. Hematological malignancies with NUP98-DDX10 are very rare. They respond poorly to conventional treatment and require allogeneic hematopoietic stem cell transplantation (allo-HSCT) to improve the prognosis.
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Objective@#To explore the association between methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C gene polymorphisms and toxicity of Methotrexate(MTX) chemotherapy in pediatric acute lymphoblastic leukemia (ALL).@*Methods@#From January 2015 to June 2018, 128 pediatric patients with ALL in southern Fujian who were admitted at the First Affiliated Hospital of Xiamen University were selected.Their peripheral blood 2 mL was collected and genomic DNA was extracted.The MTHFR genotype was detected by polymerase chain reaction(PCR) direct sequencing method, and the clinical significance of HD-MTX on ALL children with toxic and side effects was evaluated according to the National Cancer Institute-Common Toxicity Criteria.@*Results@#Among 128 children, 54 cases(42.2%) presented rash, 48 cases (37.5%)with mucosal lesions, 51 cases (39.8%) with liver function damage, 23 cases (18.0%) with renal function damage, 52 cases (40.6%) with gastrointestinal reactions, 38 cases (29.7%)with leukopenia, 34 cases (26.6%) with thrombocytopenia and 63 cases (49.2%) with hemoglobin reduction.There was no significant difference in the incidence of MTX adverse reactions (rash, mucosa lesions, liver and renal function damage, gastrointestinal reaction, leukopenia, hemoglobin decrease and thrombocytopenia) between the MTHFR C677T and A1298C polymorphisms (all P>0.05). The different clinical risk (MTX dose) of the children was not statistically signi-ficant in the MTHFR C677T and A1298C genotypes and allele frequencies (χ2=2.573, 2.264, 1.615, 0.267; all P>0.05). There was no significant difference among the abnormal incidence of MTX at 24 h, 48 h and 72 h (all P>0.05).@*Conclusions@#MTHFR C677T and A1298C polymorphisms do not seem to be good markers of MTX-related toxicity and/or outcome in pediatric ALL in southern Fujian, and its clinical application still needs further discussion.
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Objective@#To analyze the clinical efficacy and safety of thalidomide combined with conventional chemotherapy in treatment of acute leukemia by using Meta analysis.@*Methods@#Thalidomide combined with conventional chemotherapy was treated as the experiment group, chemotherapy alone was treated as the control group. Thalidomide was taken 100mg once a day, oral administration. The literatures were retrieved from PubMed, Cochrane library, Embase, China Notional Knowledge Infrastructure (CNKI),Wanfang and VIP database. The data of the randomized controlled trial (RCT) conformed to inclusion criteria were extracted, and the quality was evaluated, and then StataMP 14.0 software was used to make a Meta analysis.@*Results@#A total of 14 studies with 752 patients were included. The experiment group had a higher complete remission rate and the overall response rate compared with the control group, and the difference was statistically significant (RR= 1.61, 95% CI 1.36-1.90, P < 0.01; RR= 1.36, 95%CI 1.24-1.50, P < 0.01). The experiment group had a better efficacy in the improvement of vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR), basic fibroblast growth factor (bFGF) and bone marrow microvessel density (MVD) after the treatment compared with the control group, and the differences between the two groups were statistically significant (all P < 0.05), but there was no significant difference in the adverse events between the two groups (all P > 0.05).@*Conclusion@#Meta analysis showed that oral administration daily thalidomide 100 mg combined with conventional chemotherapy has a better clinical efficacy and antiangiogenic effect compared with chemotherapy alone, without the increase of adverse reactions.
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Objective To analyze the clinical efficacy and safety of thalidomide combined with conventional chemotherapy in treatment of acute leukemia by using Meta analysis. Methods Thalidomide combined with conventional chemotherapy was treated as the experiment group, chemotherapy alone was treated as the control group. Thalidomide was taken 100mg once a day, oral administration. The literatures were retrieved from PubMed, Cochrane library, Embase, China Notional Knowledge Infrastructure (CNKI), Wanfang and VIP database. The data of the randomized controlled trial (RCT) conformed to inclusion criteria were extracted, and the quality was evaluated, and then StataMP 14.0 software was used to make a Meta analysis. Results A total of 14 studies with 752 patients were included. The experiment group had a higher complete remission rate and the overall response rate compared with the control group, and the difference was statistically significant (RR ＝ 1.61, 95% CI 1.36-1.90, P< 0.01; RR＝ 1.36, 95% CI 1.24-1.50, P< 0.01). The experiment group had a better efficacy in the improvement of vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR), basic fibroblast growth factor (bFGF) and bone marrow microvessel density (MVD) after the treatment compared with the control group, and the differences between the two groups were statistically significant (all P <0.05), but there was no significant difference in the adverse events between the two groups (all P＞0.05). Conclusion Meta analysis showed that oral administration daily thalidomide 100 mg combined with conventional chemotherapy has a better clinical efficacy and antiangiogenic effect compared with chemotherapy alone, without the increase of adverse reactions.
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Objective To explore the association between methylenetetrahydrofolate reductase( MTHFR) C677T and A1298C gene polymorphisms and toxicity of Methotrexate(MTX)chemotherapy in pediatric acute lympho-blastic leukemia(ALL). Methods From January 2015 to June 2018,128 pediatric patients with ALL in southern Fu-jian who were admitted at the First Affiliated Hospital of Xiamen University were selected. Their peripheral blood 2 mL was collected and genomic DNA was extracted. The MTHFR genotype was detected by polymerase chain reaction(PCR) direct sequencing method,and the clinical significance of HD-MTX on ALL children with toxic and side effects was evaluated according to the National Cancer Institute-Common Toxicity Criteria. Results Among 128 children,54 cases (42. 2% )presented rash,48 cases(37. 5% )with mucosal lesions,51 cases(39. 8% )with liver function damage,23 ca-ses(18. 0% )with renal function damage,52 cases(40. 6% )with gastrointestinal reactions,38 cases(29. 7% )with leu-kopenia,34 cases(26. 6% )with thrombocytopenia and 63 cases(49. 2% )with hemoglobin reduction. There was no significant difference in the incidence of MTX adverse reactions(rash,mucosa lesions,liver and renal function damage, gastrointestinal reaction,leukopenia,hemoglobin decrease and thrombocytopenia ) between the MTHFR C677T and A1298C polymorphisms(all P>0. 05). The different clinical risk(MTX dose)of the children was not statistically signi-ficant in the MTHFR C677T and A1298C genotypes and allele frequencies( χ2 =2. 573,2. 264,1. 615,0. 267;all P>0. 05). There was no significant difference among the abnormal incidence of MTX at 24 h,48 h and 72 h(all P>0. 05). Conclusions MTHFR C677T and A1298C polymorphisms do not seem to be good markers of MTX-related toxicity and/or outcome in pediatric ALL in southern Fujian,and its clinical application still needs further discussion.
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Acute leukemia (AL) is one of the common malignant hematology diseases,which is featured with anemia,infection and hemorrhage.Chemotherapy is the main treatment of AL,but the thrombocytopenia (TCP) occurred after the chemotherapy of AL has a high incidence and a severe consequence.Therefore,its early prevention and treatment in clinic are of great importance.In this article,the treatment progress of TCP after chemotherapy in patients with AL is reviewed.
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Objective@#To explore the efficacy and safety of recombinant human interleukin-11 (rhIL-11) in treatment of chemotherapy-induced thrombocytopenia of acute leukemia.@*Methods@#Acute leukemia patients with chemotherapy-induced thrombocytopenia [Platelets (Plt) < 50×109/L] in 6 centers nationwide from February 2016 to July 2016 were treated with rhIL-11 (2 mg/time, twice per day) by subcutaneous injection. Treatment lasted 7 days or at least until Plt≥ 50×109/L. The Plt recovery was observed during treatment.@*Results@#A total of 112 patients were enrolled, and 2 patients decided to drop out of study. The efficacy population consisted of 110 patients, and the total response rate reached 74.5% (82/110). The average variation of Plt during treatment was (70±54)×109/L, and recovery average time of Plt for the patients with favorable efficacy was (8.7±3.0) days. In treatment with severe thrombocytopenia, rhIL-11 alone could shorten the recovery time compared with rhIL-11 combined with Plt transfusion [(8.0±2.6) d vs. (9.6±3.5) d, t=2.17, P=0.03].@*Conclusion@#rhIL-11 twice a day of subcutaneous injection can effectively promote Plt recovery and reduce Plt transfusion with less adverse reactions, which is worthy of further application.
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Objective@#To explore the clinical efficacy and safety of unrelated umbilical cord blood transplantation (UCBT) in the treatment of refractory and relapsed acute leukemia (AL) patients.@*Methods@#The clinical data of 22 refractory and relapsed AL patients who were treated with UCBT as salvage therapy from November 2009 to May 2017 were retrospectively analyzed. All patients received a myeloablative conditioning regimen for prevention of graft-versus-host disease (GVHD) with cyclosporine A (CSA)/short course of mycophenolate mofetil (MMF).@*Results@#①Of 22 patients, 9 cases were male and 13 female. The median age was 23 (15-44) years and median weight of 52.5 (43-82) kg. All patients were transplanted with a median umbilical cord blood nucleated cells of 3.07 (1.71-5.30)×107/kg (by weight), the median CD34+ cells was 1.60 (0.63-3.04)×105/kg (by weight). ②The myeloid cumulative implantation rate was 95.5% (95%CI 45.2-99.7%) after transplantation of 42 d, with the median implantation time of 19 (13-27) d. The platelet cumulative implantation rate after transplantation of 120 d was 81.8% (95%CI 54.2-93.6%), the median implantation time of 42 (20-164) d. ③The incidence of Ⅱ-Ⅳ, Ⅲ-Ⅳ aGVHD and the 2 year cumulative incidence of cGVHD were 36.4%, 13.6% and 40.3% respectively. ④ The transplant related mortality (TRM) after transplantation of 180d was 22.7%, 2 year cumulative rate of relapse was 18.7% (95%CI 3.6-42.5%), 2 year disease-free survival rate (DFS) and overall survival rate (OS) were 53.7% and 58.1%, respectively.@*Conclusion@#The preliminary results show that the use of UCBT is safe and effective for refractory and relapsed AL patients who fail to respond to conventional chemotherapy.
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Objective@#To determine the influence of donor-recipient sex matching on outcome of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) for acute leukemia in the setting of T-cell-replete transplants.@*Methods@#The retrospective study is based on 1 160 consecutive patients who received their first haplo-HSCT for acute leukemia between April 2002 and December 2014 at Peking University Institute of Hematology. The patients were divided into the sex-matched group and sex-mismatched group in terms of the recipient and donor sex. Then we conducted an analysis in four subgroups, male patients with male donors (M→M), male patients with female donors (F→M), female patients with female donors (F→F), and female patients with male donors (M→F). Transplant outcomes were measured in terms of hematopoietic recovery, acute graft versus host disease (aGVHD), relapse, nonrelapse mortality (NRM), disease-free survival (DFS) and overall survival (OS) in the above four subgroups. Then univariate and multivariate analysis were conducted.@*Results@#There was a higher 3-year and 5-year NRM but no difference in other transplant outcomes in sex-mismatched group when compared with the sex-matched group. F→M was compared with M→M, and the former group had higher 3-year and 5-year cumulative incidences of NRM (25.5% vs 16.1%, P=0.002; 27.1% vs 17.3%, P=0.002), decreased 5-year DFS (56.9% vs 64.4%, P=0.044), decreased 3-year OS (62.6% vs 69.8%, P=0.045). There was no significant difference in 3-year DFS and 5-year OS. There was no significant difference in grade Ⅱ-Ⅳ aGVHD and cGVHD incidence. When F→F group was compared with M→F group, only a higher grade Ⅱ-Ⅳ aGVHD incidence (43.9% vs 34.6%, P=0.047) existed. F→M was proved to be the independent risk factor influencing NRM and OS in multivariate analysis.@*Conclusion@#In haplo-HSCT for acute leukemia, the donor-recipient sex combination of male patients with female donors was of a poorer prognosis, so a male donor was a better choice for a male patient.
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Objective To study the clinical significance of serum cystatin C (Cys C) in patients with acute leukemia (AL). Methods A total of 59 newly diagnosed AL patients in Xinghua City People's Hospital from January 2014 to August 2017 were enrolled; meanwhile, 59 healthy individuals who underwent physical examination at Medical Center of Xinghua City People's Hospital were selected as the control group. AU5800 automatic biochemical analyzer from American Beckman Coulter Corporation was applied to detect the levels of serum Cys C, lactate dehydrogenase (LDH) and creatinine (Cr). The receiver operating characteristic (ROC) curve was also drawn. Results The levels of serum Cys C and LDH in AL patients were higher than those in the control group [serum Cys C: (1.36±0.72) mg/L vs. (0.76±0.27) mg/L; LDH: (456±362) U/L vs. (185±29) U/L], and there was a statistical significance (t＝-5.965, P＝0.000; t＝-5.718, P＝0.000). There was no statistical difference in the serum Cr between AL patients and control group [(86±26) μmol/L vs. (82±16) μmol/L] (P＞ 0.05). There was a positive correlation between levels of serum Cys C and LDH in AL patients (rs＝ 0.447, P < 0.05). The ROC area under curve of serum Cys C was 0.823, the standard error was 0.037, and the confidence interval of 95 % was 0.751-0.896. The ROC area under curve of serum LDH was 0.811, the standard error was 0.042, and the confidence interval of 95 % was 0.728-0.894. Conclusion The level of serum Cys C in AL patients is higher than that in the healthy population. The detection of serum Cys C is helpful in the diagnosis of AL and the evaluation of tumor burden, which is consistent with serum LDH.
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Objective To analyze the efficacy and safety of tetrandrine in the adjuvant treatment of relapsed/refractory acute leukemia (except M3).Methods A total of 58 patients with relapsed/refractory acute leukemia (except M3) admitted to six tertiary hospitals in Jiangsu Province from January 2015 to December 2017 were included in this study.The tetrandrine-adjuvant standard chemotherapy regimen and standard chemotherapy regimen were given to treatment and control groups respectively.There were 17 and 41 patients in treatment and control groups.The treatment group was given tetrandrine for 5 days before the use of standard chemotherapy.The dose of tetrandrine was 4 mg ·kg-1 ·d-1,and patients had continuous oral administration of 5 days.After that,the patients in the treatment group started chemotherapy immediately.On the other side,the control group received standard chemotherapy without any other multidrug reversal medicine.Then the clinical efficacy and safety outcomes in both groups were analyzed.Results In the treatment group,5,3,and 9 cases achieved complete remission (CR),partial remission (PR),and nonremission (NR) respectively,and the total effective (CR+PR) rate was 47.06 ％ (8/17);in the control group,14,10,and 17 cases achieved CR,PR,and NR,and the total effective rate was 58.54 ％ (24/41).There was no significant difference in the total effective rate between the two groups (x2 =0.64,P =0.424).There was no significant difference in the efficacy between the two groups of patients with different genders (P ＞ 0.05).When the disease duration was 6-11 months,the difference of efficacy between the two groups was statistically significant (P =0.041).There was no significant difference in the proportion of myeloid leukemia cells,white blood cell count,platelet count,red blood cell count,and hemoglobin between the two groups before and after treatment (all P ＞ 0.05).There was no significant difference in clinical safety indicators (urine,faecal routine,liver and kidney function,and electrocardiogram) between the two groups (all P ＞ 0.05).Conclusions Tetrandrine is more effective in patients with relapsed/refractory acute leukemia (except M3) with shorter duration of disease.Compared with chemotherapy alone,the clinical efficacy of adding tetrandrine in chemotherapy cannot be considered superior to the former.
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Objective To explore the clinical features, curative effects and prognosis of patients with psoriasis related acute leukemia. Methods The clinical data of 39 cases in the Second Hospital Shanxi Medical University from January 2011 to June 2016 were collected, and their clinical features and prognosis were analyzed retrospectively. Results Of 39 patients, 28 were males and 11 were females, with the median age of 42 years (13-76 years), the median time that suffering from psoriasis were 10 years (1-30 years); There were 23 (59.0 ％) patients with acute promyelocytic leukemia (APL), 13 (33.3 ％) patients with acute myeloid leukemia (AML) and 3 (7.7 ％) patients with B-cell acute lymphocytic leukemia (B-ALL). In patients with recurrence, there were 4 patients with APL, 4 patients with AML, and 1 patient with B-ALL. Single factor analysis showed that the type of PML-RARαfusion gene isoform and the time of suffering from psoriasis were the influencing factors of patients with APL recurrence (both P<0.05), but they were not the independent risk factors (both P>0.05) based on multivariate analysis. The complete remission (CR) rates of patients with psoriasis related APL and AML were 96％(22/23) and 46％(6/13), the 3-year overall survival (OS) rates were 96％and 44％, 3-year relapse free survival (RFS) rates were 77％and 38％, respectively. Conclusions In patients with psoriasis related acute leukemia, the largest population is APL patients, and they have a better prognosis. However, patients with psoriasis related AML and ALL have low CR rate and OS rate, and the allogeneic hematopoietic stem cell transplantation should be considered after remission.
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Objective To investigate the influence of overweight and obese on serum expressions of adipocytokines and prognosis of patients with acute leukemia. Methods Five hundred and seventy patients diagnosed as acute leukemia in the People's Hospital of Liaoning Province and Shengjing Hospital of China Medical University from July 2008 to July 2015 were collected. According to the body mass index (BMI), the patients were subdivided into two groups as obese/overweight group (BMI≥24 kg/m2) and control group (BMI<24 kg/m2). The avidinbiotincomplex-enzyme-linked immunosorbent assay (ELLSA) was used to detect the adiponectin, leptin, and resistin levels in the two groups. The t test was used to compare the difference of serum adiponectin, leptin and resistin expression between the two groups; Kaplan-Meier method was used to compare the difference of survival between the two groups. Results In patients with acute lymphoblastic leukemia (ALL)and acute myeloid leukemia (AML), the adiponectin levels in obese/overweight group were lower than those in the control group [adult ALL:(3.8±2.1) pg/ml vs. (6.4±2.9) pg/ml, child ALL:(4.2±2.7) pg/ml vs. (7.4±3.1) pg/ml, AML:(4.1±2.3) pg/ml vs. (6.9±3.1) pg/ml;t values were-2.291,-2.462,-2.244;P values were 0.023, 0.015, 0.026, respectively]. The leptin levels were high in the child ALL obese/overweight group than those in the control group (34±17 vs. 21±17) (t= 2.092, P= 0.038). The resistin levels of all the acuteleukemia patients did not have statistical difference between the obese/overweight group and control group(all P>0.05). In AML and adult ALL patients, the survival analysis showed that the 5-year overall survival rate in obese/overweight group were lower than that in the control group (38.0％vs. 46.6％,χ2= 1.449, P= 0.001;41.4％vs. 48.4％,χ2= 4.166, P= 0.041). Conclusion For the acute leukemia, the adiponectin levels are low in obese or overweight patients, and the 5-year survival rate of obese or overweight AML and adult ALL patients is lower than that of normal weight patients.
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Objective@#To investigate the influences of bone marrow stromal cells, components of extracellular matrix and cytokine secreted by stromal cells on the chemotherapeutic sensitivity of acute lymphoblastic leukemia cells to cytosine arabinoside (Ara-C).@*Methods@#The co-culture model of acute lymphoblastic leukemia cell Sup-B15 and bone marrow stromal cell OP9 was constructed. Sup-B15 cells were cultured alone or co-cultured with OP9 cells, inactivated OP9 cells, the conditional medium (CM) of co-cultured OP9 cells and Sup-B15 cells, the CM of OP9 cells alone or Sup-B15 cells alone, respectively. The effects of different concentrations of Ara-C on the proliferation of each Sup-B1 cell group mentioned above were detected by cell counting kit-8 (CCK-8) method. The effects of different concentrations of Ara-C on the apoptosis of each group were detected by flow cytometry (FCM). The expressions of Bcl-2 protein in each group were detected by western blot.@*Results@#The results of CCK-8 test showed that the inhibitory efficiency of Ara-C was in a dose-dependent manner. With different concentrations of Ara-C treatment for 48 hours, the half maximal inhibitory concentrations (IC50) of Sup-B15 and OP9 co-cultured group, Sup-B15 and inactivated OP9 co-cultured group were 0.510 and 0.339 μg/ml, respectively, significantly higher than 0.091 μg/ml of Sup-B15 cultured alone group (P<0.05). The IC50 of CM of Sup-B15 and OP9 co-cultured group was 0.204 μg/ml, significantly higher than 0.087 μg/ml of the CM of OP9 cultured alone group (P<0.05) and 0.097 μg/ml of the CM of Sup-B15 cultured alone group (P<0.05). The results of flow cytometry showed that with 0.10 μg/ml Ara-C treatment for 24 hours, the early apoptotic cell percentages of Sup-B15 and OP9 co-cultured group, Sup-B15 and inactivated OP9 co-cultured group and Sup-B15 cultured alone group were (6.67±2.19) %, (8.95±3.04) % and (20.46±2.63) %, respectively. The early apoptotic cell percentages of Sup-B15 and OP9 co-cultured group, Sup-B15 and inactivated OP9 co-cultured group were significantly lower than that of Sup-B15 cultured alone group (P<0.05). The early apoptotic cell percentages of the CM of Sup-B15 and OP9 co-cultured group, the CM of OP9 cultured alone group and the CM of Sup-B15 cultured alone group were (11.16±2.97)%, (22.08±2.71)% and (19.25±1.57)%, respectively, the former two of which were significantly lower than the last one (P<0.05). The results of western blot showed that the relative expression levels of Bcl-2 protein of Sup-B15 cultured alone group, Sup-B15 and OP9 co-cultured group, Sup-B15 and inactivated OP9 co-cultured group, the CM of Sup-B15 and OP9 co-cultured group, the CM of OP9 cultured alone group and the CM of Sup-B15 cultured alone group were 1.00±0.00, 1.53±0.03, 1.38±0.01, 1.26±0.05, 1.03±0.01 and 0.98±0.02, respectively. The expression levels of bcl-2 protein of three combined groups were significantly higher than that of Sup-B15 cultured alone group (P<0.05). while no statistically significant difference was observed between the CM of OP9 cultured alone group and the CM of Sup-B15 cultured alone group (P>0.05).@*Conclusion@#Bone marrow stromal cell OP9, the components of bone marrow extracellular matrix and cytokine secreted by stromal cells are involved in the induction of the chemotherapeutic resistance of Sup-B15 cells to Ara-C.
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Objective@#To study the expression of miRNA-181a in acute myeloid leukemia (AML) patients with normal karyotype to probe its prognosis significance.@*Methods@#The expression level of miRNA-181a in bone marrow mononuclear cells of 120 de novo AML patients with normal karyotype was detected by real time fluorescence quantitative PCR. The direct sequencing method was used to detect IDH1, IDH2, NPM1, FLT3-ITD, DNMT3A and CEBPα mutations in CN-AML patients after PCR. The relationship between miRNA-181a expression and gene mutation, the clinical parameters and prognosis were analyzed.@*Results@#The rates of overall surviva1 (OS) in high expression and low expression groups were 25.0 months and 15.0 months, respectively (P<0.05) . Relapse free survival (RFS) in high expression and low expression groups were 21.4 months and 11.2 months, respectively (P<0.05) . Significantly higher level hemoglobin, complete remission rate and proportion of wild type NPM1 expression in the high expression of miRNA-181a group were observed when compared with the lower expression of miRNA-181a group (P<0.05) . Multivariate Cox regression analysis showed miRNA-181a overexpression was an independent prognostic factor for CN-AML (HR=2.219, 95%CI 1.601~2.432, P=0.018) .@*Conclusion@#Higher expression of miRNA-181a was a good prognostic factor independent of clinical parameters and high frequency gene mutations, which implicated that the miRNA-181a expression level could be used as an important prognostic indicator of AML patients with normal karyotype.
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Objective@#To investigate the overexpression frequencies of BRE and EVI1, the correlation between BRE and EVI1 expressions and their possible clinical implications in 11q23/MLL rearrangement acute leukemia.@*Methods@#Cytogenetic examination of bone marrow cells was performed by short-term culture method. R-banding technique was used for karyotype analysis. 47 patients were detected by interphase fluorescence in situ hybridization (FISH) with dual-color break apart MLL probe. The expressions of EVI1 and BRE genes were detected by real time quantitative reverse transcription polymerase chain reaction (RQ-PCR) . The correlation and prognostic significance were statistically tested.@*Results@#11q23/MLL rearrangements were confirmed by karyotyping and FISH, respectively in 47 patients. According to immunophenotypic analyses of 37 patients, 5 patients showed positive for CD19, CD79a or CD10, 1 for CD7; the others for CD33, CD13, CD14 and CD15, and 16 of them for CD34. Of the 47 patients, 18 patients showed EVI1 overexpression and most of them presented with t (6;11) and M4/M5. The EVI1 expression was high in t (6;11) or t (9;11) subgroup comparable with levels observed in normal subgroup (P=0.038, 0.022, respectively) . 15 patients showed high BRE expression, and most of them presented with t (9;11) and M4/M5. High BRE expression was found in t (4;11) , t (6;11) , t (9;11) and t (11;19) subgroups, respectively by comparing with normal subgroup. The BRE expression was higher in t (4;11) (P=0.004) or t (9;11) (P=0.012) subgroup than in t (6;11) subgroup. Patients with EVI1 overexpression had a short survival compared with those with low EVI1 expression (P=0.049) and it also did in t (9;11) subgroup (P=0.024) . Patients with t (9;11) and high BRE expression had a long survival compared with those with t (9;11) and low BRE expression (P=0.024) .@*Conclusion@#The EVI1 overexpression was significantly frequent in acute leukemia patients with 11q23/MLL rearranged, especially within t (6;11) subgroup and M4/M5, which was associated with an inferior outcome. High BRE expression was observed frequently in 11q23/MLL-rearranged acute leukemia especially within t (9;11) subgroup and M5.
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Objective To explore the relationship between WT1 and prognosis of patients with acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL), and to evaluate the possibility of WT1 as a potential marker for monitoring the minimal residual disease (MRD). Methods Bone marrow mononuclear cells from 58 patients with primary AML, 32 patients with primary ALL, 40 patients with AML-complete remission (CR), 28 patients with ALL-CR and 31 patients with trilineage hyperplasia (control group) were collected. Real-time fluorescent quantitative PCR method was used to detect the expression of WT1 in all patients. The expression threshold of WT1 in each group was established. WT1 copy number/ABL copy number ratio×100%denotes the relative expression level of WT1 gene. Results Median relative expression level of WT1 in the control patients was much lower than that in primary AML patients [0.026%(0-0.240%) vs. 20.880 % (3.550 %-48.500 %), Z=-7.74, P20.880 %) was 60.7 % (17/28), while the CR rate was 76.7 % (23/30) in those with lower WT1 expression. WT1 expression was increased dramatically in recurrent AML patients. Relative expression level of WT1 was significantly higher in primary ALL patients [0.350 % (0.021 %-10.780 %)] compared with that in the control group Z=-2.58, P<0.05. There was no significant difference in relative expression level of WT1 between ALL and ALL-CR patients [0.038 % (0-2.800 %), P=0.065]. Conclusion WT1 expression level in AML patients is relatively high, which could be used as an effective index of prognosis evaluation and MRD monitoring for AML patients, but not for ALL patients.
ABSTRACT
Objective To investigate the expression and clinical significance of soluble E-cadherin (sE-cad) and E-cadherin (E-cad) in acute leukemia (AL), and to explore their relationship with the pathogenesis,development and diagnosis of extra-myeloid leukemia. Methods 87 newly diagnosed or relapsed AL patients (19 cases of L1, 29 L2, 14 M2, 20 M3, 4 M4, 1 M5) were collected from hospitalized patients in hematology department of Harbin Medical University Cancer Hospital. The plasma from 20 healthy volunteers was used as control group. The bone marrow was from 15 non-AL patients hospitalized in hematology department (7 cases of thrombocytopenic purpura, 4 iron deficiency anemia, and 4 fever). The expression of sE-cad in the plasma of 47 patients and 20 healthy volunteers was detected by ELISA; the expression of E-cad on the membrane surface of bone marrow MNC in 40 patients and 15 controls was determined by flow cytometry. Results The plasma level of sE-cad in AL group was significantly higher than that in healthy control group [(66.812±52.712) ng/ml vs. (17.976±14.206) ng/ml, P<0.01]. The plasma level of sE-cad in extra-myeloid infiltration AL group was significantly higher than that in no-extra-myeloid infiltration AL group [(83.545±60.759) ng/ml vs. (42.152±22.043) ng/ml, P<0.01]. The plasma level of sE-cad in high leukocytes AL group was higher than that in no-high leukocytes AL group [(85.166±57.828) ng/ml vs. (41.933±32.064) ng/ml, P<0.05]. The percentage of E-cad expression in AL group was significantly lower than that in control group [(13.615±14.038) % vs. (31.700±16.213) %, P<0.01]. The percentage of E-cad expression in no-extra-myeloid infiltration AL group was significantly higher than that in extra-myeloid leukemia infiltration AL group[(18.691±14.917) % vs. (6.589±8.959) %,P<0.01]. The percentage of E-cad in no-high-leukocytes AL group was significantly higher in high leukocytes AL group [(20.925±12.081) % vs. (7.446±11.118) %, P<0.01]. Conclusions The expression of E-cad on the membrane surface of bone marrow MNC and the expression of sE-cad in plasma may be closely associated with the occurrence of extra-myeloid leukemia and leukocytosis, which may be one of the important molecular mechanisms of leukemic cell infiltration and leukocytosis. High expression of sE-cad in plasma can be treated as one of index to diagnose extra-myeloid leukemia.