1.IL-17 regulates the expression of MHC Ⅱ and its effect on tumor growth in diffuse large B-cell lymphoma in mice
Xin XU ; Qingshan LI ; Zhigang ZHU ; Guiping CHENG ; Fang YI ; Bizhen YU
Journal of Leukemia & Lymphoma 2016;25(8):461-464,470
Objective To establish a mice model of diffuse large B-cell lymphoma (DLBCL) that was treated with adoptive immunity of Th17 cells cultured in vitro,and to analyze the relationship between IL-17 and MHC Ⅱ expression and their relation with tumor growth.Methods The CD4+CD62L+ T cells purified by MACS were stimulated under cytokine conditions including anti-CD3,anti-CD28,TGF-β and IL-6 in vitro,and SUDHL-4 cells were cultured and inoculated the SCID mice to establish DLBCL mice models.The mice were divided into Th17 cells immunity group (30 mice) and control group (20 mice).Th17 cells were injected to mice to get the adoptive immunity in immunity group,and 0.9 % NaCl in control group.The half mice were terminated at median disease onset time and median survival time,respectively.ELISA was used to detect IL-17 expression,and immunohistochemistry was applied to detect MHC Ⅱ expression in the tumor tissues.Results The median disease onset time of DLBCL mice model was 8 d,and median survival time was 28 d.The IL-17 and MHC Ⅱ expression levels in Th17 cells immunity group [(11.93±0.56) pg/ml,(69.13t0.36) %] were higher than those in control group [(9.82±0.26) pg/ml,(42.59±0.12) %] (both P< 0.000 1).Along with the progress of DLBCL,IL-17 and MHC Ⅱ expression levels were decreased [(9.53±0.18) pg/ml,(54.63±0.45) %,both P < 0.000 1].There was a significantly positive correlation between IL-17 and MHC Ⅱ (r=0.89,P=0.000).Conclusions The expression level of MHC Ⅱ can be used as a factor to judge the disease situation of DLBCL,and combination detection of the expression of both IL-17 and MHC Ⅱ will provide more reference values for judgment of the disease situation and the progress of DLBCL.
2.Progress in smoldering multiple myeloma
Journal of Leukemia & Lymphoma 2016;25(8):454-456,460
Smoldering multiple myeloma (SMM) is an asymptomatic clonal plasma cell disorder.There have been many advances in the diagnosis,prognosis and management of multiple myeloma at the 21th European Hematology Association Annual Meeting,especially SMM being discussed as a topic.These include a revised disease definition,new prognostic factors and new treatment options.
3.Expression of E-cadherin on bone marrow mononuclear cell surface and in plasma of patients with extra-myeloid leukemia and their clinical significance
Journal of Leukemia & Lymphoma 2016;25(10):599-601,617
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.
4.Effect of PTD4-GFP-Apoptin on proliferation and apoptosis in leukemia cells
Dongyang YU ; Zhuxing XIANG ; Jun SUN ; Dalin ZHANG ; Lirong HAN ; Feibo GUO ; Jiangqin SONG
Journal of Leukemia & Lymphoma 2016;25(10):577-581,598
Objective To investigate the effects of PTD4-GFP-Apoptin protein on proliferation inhibition and apoptosis-inducing of different types of leukemia cells. Methods Genetic engineering was used to restructure a carrier containing PTD4-GFP-Apoptin gene, and MTT was applied to detect the expressed PTD4-GFP-Apoptin fusion protein and its effect on the leukemia cell proliferation. Flow cytometry (FCM) was used to detect the effects on cell apoptosis. Results MTT cell proliferation inhibitory experiment showed that PTD4-GFP-Apoptin had different degree of proliferation inhibition on different types of leukemia cells;furthermore, the inhibitory effect presented positive correlation with time and concentration. FCM showed that PTD4-GFP-Apoptin had apoptosis-inducing effect on HL-60 cells, and the apoptotic rate had significant difference compared with the control group (P <0.05). Conclusions PTD4 can carry large proteins to penetrate the cell membrane, and PTD4-GFP-Apoptin may produce the inhibiting proliferation in vitro for a variety of leukemia cells. Apoptin can induce tumor cell apoptosis without affecting normal cells, which might become a new agent for the clinical treatment of leukemia.
5.Progress in allogeneic hematopoietic stem cell transplantation in treatment of hematological malignancies
Yingjun CHANG ; Yuanyuan ZHANG
Journal of Leukemia & Lymphoma 2017;26(2):65-67,82
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a curable method for hematological malignancies.Nearly all transplant candidates have donor with the successful application of haploidentical SCT.This article summarized some reports on donor selection,prophylaxis and treatment of graft-versus-host disease,and graft failure in the 58th American Society of Hematology Annual Meeting to present the progress of allo-HSCT in treating hematological malignancies.
6.Progress of 18F-FDG PET-CT in lymphoma
Wenting WANG ; Jun XIA ; Wei XU
Journal of Leukemia & Lymphoma 2017;26(2):83-85,90
PET-CT is the only current medical imaging technology to provide both metabolic and morphologic information in anatomical configuration mode,with high sensitivity and non-invasion.As one of the optimal measures in tumor diagnosis and therapy,abnormally-increased FDG uptake of some subtypes therefore makes an increasing application of PET-CT in lymphoma.The progress of PET-CT in lymphoma will be summarized in this paper based on the reports from the 58th American Society of Hematology Annual Meeting.
7.Diagnosis and treatment of primary hepatic lymphoma: report of one case
Yanli WANG ; Yuping ZHENG ; Liping SU ; Weie HAN ; Jianxin ZHANG ; Shaoling YUAN ; Xuanqin YANG ; Shengmin LAN
Journal of Leukemia & Lymphoma 2017;26(2):111-113,128
Primary hepatic lymphoma (PHL) is an extremely rare disease without any unified diagnostic criterion.The symptoms are usually nonspecific.Liver biopsy remains the most valuable tool for diagnosis of PHL.The predominant histology of PHL is diffuse large B-cell lymphoma.The therapeutic modalities are variable,including surgery,chemotherapy,radiotherapy,or combination of the various processes.This article described a 33-year-old man with diffuse large B-cell PHL who was treated at the Affiliated Cancer Hospital of Shanxi Medical Univeitity Blood Disease Diagnosis and Treatment Center in February 2014.The patient benefited from eight-cycle chemotherapy.At present,the patient is disease-free and undergoes regular follow-up.
8.Characteristics and clinical outcomes of elderly patients with acute lymphoblastic leukemia
Xilian ZHOU ; Zheng GE ; Yan GU ; Qi HAN ; Chun QIAO ; Jianyong LI
Journal of Leukemia & Lymphoma 2017;26(2):91-96,101
Objective To explore the differences in clinical and laboratory parameters between elderly and non-elderly patients with acute lymphoblastic leukemia (ALL).Poor prognostic factors in elderly patients were explored to guide the individualized treatment.Methods Two hundred and seventy-nine ALL patients were divided into two groups:elderly group with their age more than 60 years (60-79 years) and nonelderly group with their age less than 60 years (14-59 years).The differences in clinical and laboratory parameters,abnormal molecular genetics on related genes,including IKZF1,PAX5,NOTCH1,PHF6,SH2B3,LEF1,and JAK1,as well as the correlations with treatment response and clinical outcome were compared between the two groups.Results Males accounted for a smaller part in elderly group [42.9 % (21/49) vs.61.7 % (142/230),P =0.015].The percentage of B cell lineage ALL (B-ALL),Philadelphia chromosome positive (Ph+) and CD33 positive rate were higher in elderly group compared with those in non-elderly group [87.8 % (43/49) vs.70.4 % (162/230),P=0.009;47.8 % (22/49) vs.27.4 % (58/230),P=0.007;56.8 % (21/49) vs.39.0 % (64/230),P =0.049,respectively].While both lymphodenopathy and total complete remission (CR) rate gained the upper hand in non-elderly group [38.9 % (81/230) vs.20.0 % (9/49),P=0.016;91.3 % (178/195) vs.68.3 % (28/41),P< 0.001,respectively].Moreover,elderly group had lower 3-month,6-month,12-month and 24-month overall survival (OS) rates (64.6 % vs.84.4 %,P=0.001;50.0 % vs.73.8 %,P=0.001;29.2 % vs.52.4 %,P=0.003;6.2 % vs.26.2 %,P=0.003,respectively) than those of non-elderly group.No significant differences in mutation rates of PAX5,NOTCH1,PHF6,SH2B3,LEF1 and JAK1 were found (all P > 0.05).Conclusions Compared with non-elderly ALL patients,elderly ones harbor their intrinsic characteristics which might give rise to inferior outcomes.As a consequence,more attention should be poured into treating this particular group of ALL patients to improve their prognosis.
9.Effect of Dishevelled 2 on apoptosis in diffuse large B-cell lymphoma cell line OCI-Ly10
Mei CHEN ; Jun GU ; Xingzhen LIU ; Shupeng LIU ; Dongbao ZHAO
Journal of Leukemia & Lymphoma 2016;25(12):724-727,732
Objective To investigate the effects of Dishevelled (DVL) on apoptosis of diffuse large B-cell lymphoma (DLBCL) cell line OCI-Ly10, and to explore its possible mechanism. Methods Lentivirus plasmid overexpressing DVL2 was constructed, and after virus was packaged, it was transfected into OCI-Ly10 cells. Flow cytometry was used to detect the apoptosis rate of OCI-Ly10 cells with or without the stimulation by TNF-α recombinant protein. Then the gene expression of anti-apoptotic genes, GADD45β and A20, in NF-κB pathway was detected by RT-PCR. Results The virus was sucessfully transfected into OCL-Ly10 cells which overexpressed DVL2. The apoptosis rate of OCL-Ly10 cells overexpressing DVL2 without the stimulation by TNF-α was increased compared with that of the negative control group [(15.46 ±2.37) % vs. (11.72±3.53)%, P=0.03], the A20 mRNA expression level was decreased compared with that of the negative control group [(0.66 ±0.01) vs. 1, P=0.04], and the relative expression level of GADD45β mRNA was not significantly decreased compared with that of the negative control group [(0.79 ±0.15) vs. 1, P=0.642]. The apoptosis rate of DVL2 overexpression OCI-Ly10 cells stimulated by TNF-α was significantly higher than that of the negative control group treated by TNF-α [(22.78±4.56)%vs. (12.79±2.89)%, P=0.007]. The gene expression of A20 and GADD45β in DVL2 overexpression cells stimulated by TNF-α was significantly increased, however, the magnitude of increase in DVL2 overexpression cells was less than that in the negative control group treated by TNF-α [A20: (3.75 ±0.14) times vs. (6.89 ±0.10) times, P=0.008; GADD45β:(4.750±0.21) times vs. (6.14±0.08) times, P=0.03]. Conclusion DVL can promote the apoptosis of OCI-Ly10 cells, and its mechanism may be related with anti-apoptotic genes that inhibits its downstream via NF-κB pathway.
10.Primary diffuse large B-cell lymphoma of central nervous system:clinical characteristics and prognostic analysis
Lianjie HU ; Fengyang LIN ; Xiaogong LIANG ; Wei LI ; Hong ZHANG ; Yongqian JIA
Journal of Leukemia & Lymphoma 2017;26(1):28-32,36
Objective To investigate the clinical characteristics and prognosis of primary diffuse large B-cell lymphoma of central nervous system ( PCNS DLBCL). Methods The data of 70 patients with PCNS DLBCL confirmed by pathology were retrospectively analyzed. Survival and prognostic analyses were further conducted in the 66 follow-up patients. Results Median age at diagnosis was 57 years old. The ratio of male and female was 1.3∶1. The time from having symptoms to seeking medical advice was less than 2 months in 54 (77.1%) patients. 44 (62.9 %) patients had increased intracranial pressure, and 26 (37.1 %) patients had limb weakness or hemiplegia symptoms. 37 (52.9%) patients were multiple lesions, 59 (84.3%) cases were supratentorial, and 46 (65.7%) cases showed involvement of deep-brain tissues. Among 66 follow-up patients 7 cases received supportive and palliative care, 27 cases received surgery, 6 cases received radiotherapy, 9 cases received chemotherapy alone, and 21 cases received radiotherapy in addition to chemotherapy. The median overall survival (OS) was 9 months (95 % CI 1-16 months), and the 2-year survival rate was 36.1 %. The median OSs of the supportive and palliative therapy group and the surgery group were 2 months and 3 months, respectively. The median OS of the chemotherapy, radiotherapy or combination group was 33 months (95%CI 22-43 months) and the 2-year OS rate was 56.9 %. The Cox multivariate regression analysis showed that the involvement of deep-brain tissues (P=0.04) and not receiving radiotherapy or chemotherapy (P=0.00) were related to poor prognosis. Conclusions PCNS DLBCL is a highly aggressive and malignant tumor. Patients undergoing only surgery have poor effect and short survival. The patients with involvement of deep brain tissues have a poor prognosis. The chemotherapy, radiotherapy or combination of them may improve the prognosis.