1.Treatment of lymphoblastic leukemia with CD19-specific modified chimeric antigen receptor T cells.
Huan-Huan LI ; Ping ZHU ; Xue-Qiang WU ; Yu-Feng LIU
Journal of Experimental Hematology 2014;22(6):1753-1756
Bioengineered T cells, which are the genetically manipulated T cells to express chimeric antigen receptor T Cell (CAR T) against leukemia-associated specific antigens, were applied to treat acute and chronic lymphocytic leukemia with CAR T. CAR T cells combined with cell-surface binding site and anti-CD19 chimeric antigen receptor can treat diseases through T cells transfection. CAR T cells can recognize the CD19 antigen on B cells with specific cell-surface loci. CAR T cells can proliferate by 1000 times and differentiate in vivo by the CD19 antigen stimulation, therefore, kill the acute and chronic lymphocytic leukemia cells effectively. This article briefly reviews the CAR T cells and the effect of CAR T cells on acute and chronic lymphoblastic leukemia.
Animals
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Antigens, CD19
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B-Lymphocytes
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Humans
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Immunotherapy, Adoptive
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Precursor Cell Lymphoblastic Leukemia-Lymphoma
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immunology
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therapy
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Receptors, Antigen, T-Cell
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immunology
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T-Lymphocytes
2.Progress of study on drug therapy in adults patients with acute myeloid leukemia (non APL) after remission.
Journal of Experimental Hematology 2014;22(6):1748-1752
Acute myeloid leukemia (non APL) is a group of highly heterogeneous hematologic malignancy.In recent years, after the standard "3+7" regimen, the complete remission rate of adult patients with AML (non-APL) can be as high as 70%-80%. However, due to the existence of minimal residual disease after remission, the recurrence of the disease still inevitable, only approximately 20% to 30% of the patients enjoy longterm disease-free survival. Currently only allogeneic hematopoietic stem cell transplantation is one of the most effective treatment ways for AML. The number of transplant patients is limited, because of various reasons, such as the physical condition of patients, donor sources or economic reason. After transplantation, patients also have the possibility of recurrence, therefore, drug treatment is still important after AML remission. At present, NCCN (National Comprehensive Cancer Network) recommended high-dose cytarabine as first-line postremission therapy for patients of good prognosis group and as second-line therapy for intermediate risk group. In recent years, researchers have explored other drugs, such as the nucleoside analogues, methyltransferase inhibitors and protease inhibitors or other drugs for the treatment of adult AML patients who is in remission.In this article, the treatment of conventional medicine for the treatment of AML after complete remission is summarized.
Cytarabine
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Disease-Free Survival
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Hematopoietic Stem Cell Transplantation
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Humans
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Leukemia, Myeloid
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Leukemia, Myeloid, Acute
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drug therapy
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Remission Induction
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Treatment Outcome
3.Expression and Significance of PTPL1 in Hematological Malignancies.
Wen-Ming WANG ; Jing WANG ; Hong-Mei JING
Journal of Experimental Hematology 2014;22(6):1744-1747
PTPL1 is a protein with a predicted MW of 270 kD, and plays a major role in many cellular functions, including cell survival, proliferation, differentiation and motility. Evidence has demonstrated that PTPL1 is associated with tumor. Although many conflicting results suggested that PTPL1 has two contradictory effects (supressing or promoting ) on tumor, the real effect depends on the involved substrate and the cellular context. Expression of PTPL1 is low in lymphoma, while it is high in myeloid leukemia. PTPL1 has been regarded as a tumor suppressor in lymphoma, the methylation of PTPL1 promoter leads to gene expression reduced or disappeared, playing a lymphoma tumor suppressor role. This review focuses on PTPL1 domain and its interacting proteins, the relationship between PTPL1 and hematological malignancies.
Cell Movement
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Cell Survival
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Genes, Tumor Suppressor
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Hematologic Neoplasms
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genetics
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metabolism
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pathology
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Humans
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Protein Tyrosine Phosphatase, Non-Receptor Type 13
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genetics
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metabolism
4.Significance of chromosome 7 abnormalities in myeloid malignancies.
Wen-Hui SHI ; Xiao LI ; Chun-Kang CHANG
Journal of Experimental Hematology 2014;22(6):1739-1743
Chromosome 7 abnormalities are the most common cytogenetic alterations found in myeloid malignancies. Myeloid malignancies exhibiting monosomy 7/del (7q) have been confirmed to associate with high susceptibility to infections, poor response to chemotherapy, and short survival time, so speculating that chromosome 7 has important tumor suppressor genes. Commonly deleted segments (such as 7q22) of chromosome 7 have been identified by FISH and other technologies. Genes (EZH2, MLL5, DOCK4, SAMD9L/SAMD9) located in commonly deleted segments of 7q have been cloned and characterized along with the advance of molecular biology.This review summaries the current advancement about myeloid malignancies associated with monosomy7/del(7q).
Chromosome Deletion
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Chromosomes, Human, Pair 7
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Humans
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Leukemia, Myeloid
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genetics
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Myeloproliferative Disorders
5.Analysis of gene expression profiles to improve the treatment of leukemia.
Journal of Experimental Hematology 2014;22(6):1735-1738
In clinical practice, acute myelocytic leukemia (AML) has been classified into favorable risk type, intermediate risk type and unfavorable risk type in order to take a proper treatment and good prognosis. Unfortunately, the majority of AML patients are defined as an intermediated risk and they have diverse responses to standard therapy. Some of them should accept the allogeneic hematopoietic stem cell transplantation after first induction remission to improve prognosis, but others can survive through the chemotherapy based on consolidation regimens. However, with the advanced high-throughput sequencing technology, people tend to view the complex interplay as a whole instead of investigating the abnormality independently. The gene expression profile consisting of variation of methylation, mRNA, microRNA and other information contribute to further specify the leukemia subtype and improve the treatment and prognosis of leukemia. Moreover, the gene expression profile can help to know more about the essential of the disease and to develop the new drug which is more effective and specific.
Gene Expression Regulation, Neoplastic
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Humans
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Leukemia, Myeloid, Acute
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genetics
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Prognosis
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Transcriptome
6.Establishment of real-time fluorescent quantitative polymerase chain reaction for rapid detection of M244V mutation in kinase domain of BCR-ABL fusion gene.
Qi HUANG ; Xin DU ; Qiao-Xia ZHANG ; Jia-Cai ZHUO
Journal of Experimental Hematology 2014;22(6):1728-1734
The present study was aimed to establish a high sensitive and specific method for detecting M244V mutation in kinase domain of BCR-ABL(fusion gene) by using real-time quantitative PCR technology. The specific primer of the mutational site was designed, and then the PCR reaction system and condition were optimized to establish the new real-time PCR method for detecting M244V mutation. The results showed that a method of detecting M244V mutation has been successfully established. The detection results indicated that this method possessed high sensitivity, specificity and accuracy. It is concluded that the method based on fluorescent quantitative polymerase chain reaction for detecting M244V mutation can be used to detect the M244V mutation in CML patients successfully.
DNA Primers
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Fusion Proteins, bcr-abl
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genetics
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Humans
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Mutation
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Real-Time Polymerase Chain Reaction
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methods
7.Influence of reagent storage in Sysmex CA7000 for different time on 4 test RESULTS: of the plasma coagulation.
Journal of Experimental Hematology 2014;22(6):1721-1727
The purpose of this study was to investigate the influence of blood coagulation reagents stored for different time on test results of the specimens prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and fibrinogen (Fib). A total of 21 patient plasma specimens was taken and measured for homeostasis by Sysmex CA7000 automated blood coagulation analyzer and supporting reagent. The PT, APTT, TT and Fib of specimens were measured with the reagents stored in Sysmex CA7000 for different time. The differences of PT, APTT, TT and Fib were analyzed between values measured of the reagents stored for 0 hour and different time (TS:12, 24, 36,48, 60, 72 h; DA:24, 48, 72, 96, 120 h; TT:2, 4, 6, 8, 10, 12 h; TR:4, 8, 12, 16, 20, 24 h; OVB:1, 2, 3, 4, 5 ,6 h), respectively. The results showed that when coagulation reagent TS were stored for more than 48 h , DA 96 h, TT 10 h, TR 16 h and OVB 4 h, the values of PT, APTT, TT and Fib of samples were statistically different from the values measured with fresh coagulation reagent (P < 0.01), respectively. Compared 0 h with TS stored for 48-72, DA 96-120, TT 10-12, TR 16-24 and OVB 4-6 h, the percentage difference of PT, APTT, TT and Fib is in -2.6% ∼ 10.8%, -3.44% ∼ 4.8%, -3.9% ∼ 5.52%, -10.8% ∼ 3.3% and -17.2% ∼ 0.5%, the PT and Fib changes were more significant. Accordingly, the result of PT, APTT and TT had a uptrend as the reagent stored in Sysmex CA7000 analyzer for a long time, while Fib downtrend. It is concluded that the reagents showed be timely replaced when the plasma coagulation test is performed so as to obtain accurate results of examination.
Blood Coagulation
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Blood Coagulation Tests
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Blood Preservation
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methods
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Fibrinogen
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Hemostasis
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Humans
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Indicators and Reagents
8.Blood matching and transfusion for 12 acute autoimmune hemolytic anemia patients by extracorporal hemolysis test.
Min YUAN ; Cong-Hai TANG ; A-Yang WU ; Hui-Cong YANG ; Wei-Wei GAN ; Tian-Xin ZHANG ; Yan-Xue HUANG ; Wei-Ping XU
Journal of Experimental Hematology 2014;22(6):1716-1720
In order to screen the compatible red cells by using extracorporal hemolysis test for acute autoimmune hemolytic anemia (AIHA) patients who were difficult to be matched by automatic microcolumn gel indirect antiglobulin test. Twenty-six cases of AIHA were chosen as control group, to whom the same type of donor red blood cells were infused with the weakest blood agglutination; 12 cases of acute AIHA patients were chosen as test group, these patients were difficult to be matched by automatic microcolumn gel indirect antiglobulin test, and the donor red cells without hemolysis by extracoral hemolysis test were transfused for them. The results showed that compared with the control group,the effect of transfusion was better in test group (P < 0.01), with 2.26 U leukocyte-depleted erythrocyte suspension in average, whose hemoglobin, reticulocyte and total bilirubin levels were changed significantly compared with those before blood transfusion (P < 0.01) . It is concluded that the compatible red blood cells for the acute AIHA patients can be screened by the extracorporal hemolysis test, when it is difficult to screen by the automatic microcolumn gel indirect antiglobulin test.
Anemia, Hemolytic, Autoimmune
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therapy
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Blood Transfusion
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Coombs Test
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Erythrocyte Count
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Erythrocytes
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Hemolysis
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Humans
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Platelet Transfusion
9.Isolation, culture and characterization of outgrowth endothelial cells from the human peripheral blood.
Jie YIN ; Zhen-Ni MA ; Xiao-Juan ZHAO ; Chang-Geng RUAN
Journal of Experimental Hematology 2014;22(6):1711-1715
Compared with endothelial progenitor cells, outgrowth endothelial cells (BOECs) from peripheral blood are rich in protein for blood angiogenesis and cell adhesion, similar to mature endothelial cells in biological characteristics. Moreover, they are now replacing human umbilical vein endothelial cells for the latter's limited life span and drift of phenotype, and might become a new tool for exploring the vascular abnormalities. This study was aimed to establish the protocol of producing BOECs, and then analyze the cell phenotype and function of BOECs. Mononuclear cells were collected from peripheral blood by gradient centrifugation and then seeded on plates and cultivated in EGM-2 medium for 4 weeks. The morphological changes of cells were observed and cell phenotype was examined by flow cytometry. VWF multimers were used to analyse the distribution of vWF multimers in superment of BOECs and the storage of vWF in BOECs, and the secretion of vWF in BOECs under stimulation was detected by confocal fluorescence microscopy. The results showed that after 4-week-culture in vitro, the cell colonies and characteristic cobblestone-like morphology of BOECs were found in plates. For another three weeks of expansion, BOECs expressed CD31, CD34, and EPCR, without the expression of CD14, CD45 and CD133. The vWF from BOECs cell supernatant shared the same multimer pattern as that in normal plasma. By confocal fluorescence microscopy, vWFs were observed in BOECs. The amount of vWF increased in cells, and vWF strings were formed on cell surface by the stimulation of phorbol-12-myristate-13-acetate(PMA). It is concluded that the BOECs are first successfully established, and the phenotype and function of BOECs are analyzed. They are the native cell models for the pathogenesis of von Willebrand diseases (vWD), and may be used as new gene therapy tools for vWD.
Cell Adhesion
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Cell Count
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Cell Culture Techniques
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methods
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Cell Proliferation
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Cell Separation
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methods
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Cells, Cultured
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Endothelial Cells
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cytology
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Flow Cytometry
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Humans
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Phenotype
10.Kinetics of Cu crossing human erythrocyte membrane.
Journal of Experimental Hematology 2014;22(6):1707-1710
This study was aimed to investigate various factors influencing the proceduction of Cu(II) crossing human erythrocyte membrane, including concentration of Cu²⁺, pH value of the medium, temperature and time of incubation, and to derive kinetic equation of Cu(II) crossing human erythrocyte membrane. Suspension red blood cells were incubated by Cu²⁺, then content of Cu²⁺ crossed human erythrocyte membrane was determined by atomic absorption spectrometry under various conditions after digestion. The results showed that content of Cu²⁺ crossed human erythrocyte membrane increased with the increase of extracellular Cu²⁺ and enhancement of incubation temperature, and the content of Cu²⁺ crossed human erythrocyte membrane showed a increasing tendency when pH reached to 6.2-7.4, and to maximum at pH 7.4, then gradually decreased at range of pH 7.4-9.2. It is concluded that the Cu²⁺ crossing human erythrocyte has been confirmed to be the first order kinetics characteristics within 120 min, and the linear equation is 10³ × Y = 0.0497t +6.5992.
Copper
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pharmacology
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Erythrocyte Membrane
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drug effects
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Humans
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Hydrogen-Ion Concentration
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Kinetics
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Temperature