Drug Delivery Systems ; Humans ; Lymphoma ; drug therapy

Chronic myeloid leukemia (CML) has made a milestone progress due to the development of the first generation tyrosine kinase inhibitor(TKI). Nowadays, most clinical trials in CML focus on discontinuation, even the second discontinuation, and the third generation TKI against T315I mutation. The conventional treatments are more focused on decreasing BCR-ABL transcripts rapidly. At the same time, the treatment management of some special patients has been valued.

Antineoplastic Agents ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Arsenicals ; administration & dosage ; therapeutic use ; Humans ; Leukemia, Promyelocytic, Acute ; drug therapy ; Oxides ; administration & dosage ; therapeutic use ; Tretinoin ; administration & dosage

OBJECTIVETo detect the mutations of AML/MDS- related genes by using next generation sequencing (NGS), to analyze the mutation levels of each genes in the AML/MDS and the sensitivity of NGS, and to evaluate the feasibility of gene mutations for monitoring the MRD and predicating the progression of diseases.

METHODSThe specimens were collected from primary AML (68 cases) and MDS (57 cases) patients from August 2015 to June 2016 in the Harbin Institute of Hematology and Oncology. The mutations of 22 related genes were detected by using AML/MDS-NGS chips.

RESULTSTET2 gene showed the highest mutation rate in AML (55.9%) and MDS (56.1%). The gene mutations were as follows: CEBPA (11.8%), DNMT3A (7.4%), C-KIT (7.4%) and FLT3-ITD (7.4%) in AML, and U2AF1 (10.5%) and SRSF2 (10.5%) in MDS. All the genes had specific mutation sites except TP53 and CEBPA. The mutations of FLT3, C-KIT and CEBPA became negative in the 5 AML patients in remission when compared with those at primary attack, but the mutation rate of TET2 gene was not obviously changed, whereas the mutation rate of the 5 MDS patients was not significantly changed. The new gene mutations appeared in 3 MDS patients with disease progression, but the mutation rate was not changed significantly in the disease progression. The gene mutation rate still has not been changed significantly even after remission.

CONCLUSIONBoth AML and MDS have their own specific mutated genes and sites. Some gene mutations, such as CEBPA, can be used as an effective indicator to monitoring MRD in AML patients, but those only used for the evaluation of the disease progression and prognosis in MDS patients.

Adult ; Aged ; Arsenicals ; pharmacology ; therapeutic use ; Bone Marrow Cells ; drug effects ; metabolism ; DNA Methylation ; drug effects ; Female ; Humans ; Inhibitor of Differentiation Proteins ; metabolism ; Male ; Middle Aged ; Myelodysplastic Syndromes ; metabolism ; therapy ; Oxides ; pharmacology ; therapeutic use ; Treatment Outcome ; Young Adult

OBJECTIVETo retrospectively analyze the immunophenotyping, fusion gene and gene mutation of 30 acute lymphoblastic leukemia (ALL) cases and to investigate the relationship between the analysis results and the clinical therapeutic effect and prognosis.

METHODSThirty All phtients were collected from the First Hospital of Harbin, Institute of Hematology and Oncology Department of Pediatrics from August 2015 to June 2016. According to the classification of FAB standard, 27 cases were B system ALL, 3 cases were T system ALL. All patients were diagnosed by bone marrow cell morphology, immunophenotype, cytogenetics and molecular biology detetions, the differentiation antigens on membrane surface and in cytoplasm of ALL cells, and 43 kinds of fusion gene qualitative screening（BCR-ABL， AML1-ETO, PML-RARα and so on） were qualitative screened and ALL gene mutations（IKZF1, TP53, PAX5, JAK1, JAK2, CRLF2, PHF6, NOTCH1, FBXW7, PTEN）were detected by next generation sequencing(NGS).

RESULTS(1) Among 30 ALL patients, the incidence of B-ALL(90.00%) was higher than that of T-ALL(10.00%). (2) 27 cases of B-ALL expressed CD19, CD22, CD10, CD34 and so on. CD19 and CD22 were the most diagnostic antigens of B-ALL. (3) 3 cases of T-ALL mainly expressed cCD3, CD7, CD10, cTDT and so on; cCD3 and CD7 were the most diagnostic antigens of T-ALL. (4) The quantitative screening of 30 cases of ALL 43 fusion genes found BCR-ABL,TEL-AML1 and E2A-PBX1, MLL-AF6, MLL-AF4, and SIL-TAL1 fusion gene was positive in 1 case each; NGS detection of gane mutations associated with ALL showed that: 3 cases of B-ALL found that TP53 mutation occured 3 casas of B-ALL, TET2 I1762V mutations in 1 cases, 3 patients (2 cases of T-ALL, 1 cases of B-ALL) showed NOTCH1 gene mutation. After a cycle of treatment, the efficacy of adult B-ALL treatment (28.57%) was significantly lower than that of child B-ALL (95.00%), and the survival rate of child B-ALL was significantly better than that of adult B-ALL until July 10, 2017, and the differences were significant.

CONCLUSIONThe immunophenotype technology of leukemia and molecular biology has an important guiding role in the diagnosis of leukemia, selection of treatment plan and evaluation of curative effect, and it is the complement of bone marrow cell morphology diagnosis.

Humans ; Immunophenotyping ; Oncogene Proteins, Fusion ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Retrospective Studies

OBJECTIVE: To investigate the effect of Quercetin (Qu) on cell proliferation, apoptosis and cell cycle, as well as the expression changes of Wnt/β-catenin signaling pathway, apoptosis and cell cycle regulators and BCR-ABL in CML susceptible cells K562 and imatinib-resistant cells (IM) K562R. METHODS: The trypan blue staining was used to detect the all proliferation. The cell cycle and apoptosis were detected by flow cytometry. The fluorescence quantitative PCR and Western blot were used to detect the expression of mRNA and protein respectively. RESULTS: After administration with 5, 10, 20, 40, 80, 160, 320 μmol/L Qu, the inhibition ratio in K562 cells was 5.07%, 5.98%, 11.09%, 31.88%, 56.89%, 70.44%, 86.63%; and that in K562R cells were 4.99%, 9.75%, 10.54%, 8.93%, 25.13%, 46.89%, 68.60%; IC of K562 and K562R was 76.4 μmol/L and 230.2 μmol/L, respectively. Flow cytometry showed that Qu (50, 100 and 200 μmol/L) could induce cell apoptosis and cell cycle arrest in a dose-dependent manner (r=0.9914, r=0.9871 respectively). After treatment with Qu (100 μmol/L)，the expressions of mRNA (P＜0.05) and protein(except Caspase-9) expression of Caspase-3, 8 and 9, p21 and p27 increased in K562 cells as compared with control, but the protein expression of p27 and Caspase-3 not changed in K562R. Qu (100 μmol/L) could decrease the mRNA(P＜0.05) and protein levels of Wnt/β-catenin signaling pathway members GSK-3β, β-catenin, Lef-1 and the downstream targets PPAR-δ and Cyclin D1 compared with control. The PCR results showed that Qu could reduce the BCR-ABL mRNA expression in CML cells, but the protein expression of BCR-ABL and p-BCR-ABL not obviouly changed. CONCLUSION Qu can inhibit the proliferation K562 and K562R cells, and decrease the drug resistance and increase the sensitivity, that relate with inhibiting Wnt/β-catenin signaling pathway, activating apoptosis pathway and cyclins.
Apoptosis ; Cell Proliferation ; Drug Resistance, Neoplasm ; Glycogen Synthase Kinase 3 beta ; Humans ; K562 Cells ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Quercetin ; Wnt Signaling Pathway ; drug effects ; beta Catenin

According to the clinical needs of precise radiotherapy, an integrative thermoplastic immobilization board for radiotherapy was developed for the purpose of immobilizing head position, head, neck and shoulder positions and body position respectively. The new style board has several characteristics: a board with multi-purposes, ease of handling and good accuracy of patients' positions, etc.
Equipment Design ; Humans ; Immobilization ; Posture ; Radiotherapy ; instrumentation

OBJECTIVE: To explore the coagulation deficit and genetic basis for a Chinese pedigree affected with Congenital dysfibrinogenemia (CD). METHODS: Peripheral venous blood samples of the proband and her family members (including 4 individuals from three generations) were subjected to routine blood test and assays of liver and kidney functions and viral hepatitis to exclude related diseases. Clauss method and DFg-PT method were used to determine the fibrinogen activity (Fg:C), and an immunoturbidimetric assay was used to determine the level of fibrinogen antigen (Fg:Ag). All of the exons (22 in total) and their flanking sequences of the FGA, FGB and FGG genes were amplified by PCR and directly sequenced. Variants in the coding regions of the three genes and transcriptional splicing sites were screened by using Mutation Surveyor^TM software. RESULTS: The Clauss method showed that Fg:C was significantly reduced in the proband and her father, whilst her mother and son were normal. With the DFg-PT method, the proband, her parents and son were all within the normal range. The Fg:C/Fg:Ag ratio of the proband and her father was lower than 0.7, whilst her mother and son were above 0.7. No significant change in the prothrombin time, activated partial thromboplastin clotting time and thrombin time was noted. Two genetic variants were detected, which included a homozygous missense variant in the FGA gene [c.991A>G (p.Thr331Ala)], which was predicted to be benign, and a heterozygous missense variant of the γ chain of the FGG gene [c.1211C>G (p.Ser404Phe)], which is located in a conserved region and unreported in the CLINVAR/HGMD/EXAC/1000G databases and literature. CONCLUSION This pedigree has conformed to the autosomal dominant inheritance of CD. The c.1211C>T (p.Ser404Phe) missense variant of the γ chain of the FGG gene probably underlay the pathogenesis of CD in this pedigree. The variant was unreported previously and named as "Fibrinogen Harbin II Ser404Phe".
Female ; Humans ; Afibrinogenemia/congenital* ; East Asian People ; Fibrinogen/genetics* ; Mothers ; Mutation ; Pedigree

BACKGROUNDTo investigate whether Borna disease virus (BDV) infection is related to the schizophrenic patients from China.

METHODSA reliable Western-blot method for detection of BDV-p24 antibody was established by adjusting the reaction conditions of BDV-p24 recombinant protein and specific antibodies. The sera of schizophrenic patients and normal controls from Heilongjiang Province were screened for specific BDV-p24 antibody by this method, and the BDV-p24 antibody positive sera were confirmed by the Western-blot method with sera-GST protein absorption.

RESULTSTen of 116 (8.6%) schizophrenic patients were found to be positive for BDV-p24 specific antibody, while no BDV-p24 specific antibody was found in sera of normal controls.

CONCLUSIONSThe results demonstrate that the Borna disease virus infection also exists in China, and the infection is possibly associated with schizophrenia in some way.

Antibodies, Viral ; blood ; Blotting, Western ; Borna disease virus ; isolation & purification ; Humans ; Schizophrenia ; virology ; Viral Proteins ; immunology