2.The detection and significance of high mobility group box chromosomal protein 1, RORγt and inter leukin-17 in peripheral blood of rheumatoid arthritis
Yan SHI ; Shengjun WANG ; Jianguo CHEN ; Yuan XUE ; Zhiqiang HE ; Chenglin ZHOU ; Dong ZHENG ; Heng YANG ; Yazhen LI ; Jia TONG ; Zhaoliang SU ; Qixiang SHAO ; Huaxi XU
Chinese Journal of Rheumatology 2010;14(3):147-150
Objective To detect the expression levels of high mobility group box chromosomal protein 1 (HMGB1) and Th17 cells transcription factors, related cytokines in peripheral blood of rheumatoid arthritis (RA) patients and analyze the relations between HMGB1 and CRP, ESR, RF in RA patients. The other aim of this study is to identify the expression level of HMGBI and the relationship between HMGB1 and Th17 in RA patients. Methods The mRNA levels of HMGB1, RORyt, interleukin (IL)-17 in the peripheral blood mononuclear cells (PBMC) were determined by quantitative real-time PCR (QRT-PCR) from 80 patients with rheumatoid arthritis,including 32 RA patients in stable phase and 48 patients in active phase, and 50 healthy volunteers. The concentration of HMGB1, IL-23, IL-17 in plasma were detected by enzyme linked immunosorbent assay (ELISA), one-way ANOVA and Spearman's correleation were adopted for statistical analysis.Results The mRNAs of HMGBI, RORyt and IL-17 in RA patients were higher than that in healthy control group (P<0.05), especially in active RA patients [ HMGB 1 (0.424±0.262) pg/ml, RORγt (0.34±0.25) pg/ml,IL-17 (1.42±0.38) pg/ml,P<0.01 ] when compared with patients with stable disease. The concentration of HMGB1, IL-23 and IL-17 in the plasma of RA patients was higher than that of the healthy control group (P< 0.05), and was positively correlated with the expression levels of HMGB1, Th 17-associated factors and the level of CRP, ESR, RF in RA patients' plasma(P<0.05). Conclusion The HMGB1 and Thl7 cells levels are higher in active RA patients than those in patients with stable disease, arid there is significant positive correlation between them. Detection of peripheral HMGB1 and Thl7 cell-specific transcription factors or related cytokines can help to understand the development and progress of rheumatoid arthritis and provide clues for new treatment targets for RA.
3.Effect of oleic acid and isosorbide mononitrate loading on the phase diagrams and in vitro release profiles of glyceryl monooleate liquid crystalline system
Xingyi ZHANG ; Di MA ; Yazhen ZHENG ; Liang XU ; Yuan GAO
Journal of China Pharmaceutical University 2016;47(5):581-586
The aim of the study was to investigate the effect of oleic acid(OA)and isosorbide mononitrate(ISMN)on the phase diagrams of glyceryl monooleate(GMO)liquid crystalline systems and release of ISMN from them. Liquid crystalline systems of GMO/H2O, GMO/H2O/ISMN and GMO/H2O/OA were prepared and their phase diagrams were plotted. Investigation of water absorption of GMO and ISMN release profiles shown that the release mechanism of ISMN was diffusion-controlled. Increased drug loading accelerated the release rate. However, the increased loading of OA decreased ISMN release. The result could offer practical basis for drug loading and the selection of additives in GMO liquid crystalline system.
4.Evolvement of a five-way translocation t(5;9;22;6;17) from a four-way Philadelphia translocation t(5;9;22;6) in a rare case of chronic myeloid leukemia.
Shu KONG ; Yuqing GU ; Yazhen QIN ; Zheng WANG ; Lin FENG ; Qian JIANG ; Yueyun LAI
Chinese Journal of Medical Genetics 2020;37(12):1395-1398
OBJECTIVE:
To trace a rare case of chronic myeloid leukemia (CML) with a four-way Philadelphia chromosome variant by cytogenetic analysis in order to provide a basis for the selection of treatment.
METHODS:
Bone marrow morphology, chromosomal karyotyping, fluorescence in situ hybridization (FISH) and real-time quantitative PCR (RQ-PCR) were used for the diagnosis and staging of the disease. Point mutations in the tyrosine kinase domain of ABL1 gene were detected by Sanger sequencing.
RESULTS:
The patient was initially diagnosed as CML in chronic phase (CML-CP) with a chromosomal karyotype of 46,XX,t(5;9;22;6)(q13;q34;q11;q25), while FISH revealed presence of a variant Philadelphia chromosome translocation. Clonal evolution has occurred after 38 months of tyrosine kinase inhibitor (TKI) treatment, when cytogenetic analysis revealed coexisting t(5;9;22;6)(q13;q34;q11;q25) and t(5;9;22;6;17)(q13;q34;q11;q25;q11). After 57 months of TKIs treatment, only the t(5;9;22;6;17) clone was detected. Three months later, hyperdiploidy with additional abnormalities were detected in addition to t(5;9;22;6;17). Three mutations, including p.Tyr253Phe, p.Thr315Ile and p.Gly250Glu, were identified in the tyrosine kinase domain of the ABL1 gene during the course of disease. The patient did not attain cytogenetic and molecular response to TKIs.
CONCLUSION
The four-way variant translocation may be genetically unstable. Clonal evolution and genetic mutations are likely to occur during TKIs treatment, resulting in poor response to drug therapy. This observation, however, needs to be confirmed by large-scale studies.
Enzyme Inhibitors/therapeutic use*
;
Evolution, Molecular
;
Female
;
Humans
;
In Situ Hybridization, Fluorescence
;
Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics*
;
Mutation/genetics*
;
Philadelphia Chromosome
;
Translocation, Genetic
5. Comparative study of cytogenetic response evaluated by conventional banding analysis and fluorescence in situ hybridization in chronic myeloid leukemia patients during tyrosine kinase inhibitor treatment
Zheng WANG ; Na LI ; Lu GAO ; Lin FENG ; Yazhen QIN ; Hui DANG ; Yan SHI ; Qi HE ; Qian JIANG ; Hao JIANG ; Yueyun LAI
Chinese Journal of Hematology 2017;38(11):962-967
Objective:
To compare the cytogenetic response detected by conventional banding analysis (CBA) and fluorescence in situ hybridization (FISH) and to explore the correlation between the cytogenetic and molecular response in chronic myeloid leukemia (CML) patients during tyrosine kinase inhibitor (TKI) treatment.
Methods:
CBA, FISH and real-time quantitative reverse transcriptase polymerase chain reaction (RQ-PCR) methods were performed to detect the cytogenetic and molecular response simultaneously in 504 bone marrow samples from 367 CML patients who received TKI treatment.
Results:
Among 504 samples, 344 were detected to reach complete cytogenetic response (CCyR) by CBA, while 297 samples reached CCyR by FISH which were considered to carry BCR-ABL positive cells<1%. When the results of CBA, FISH and RQ-PCR were compared in 493 samples at the same time, it showed that in 337 samples with CBA-CCyR, 273 (81.0%) reached FISH-CCyR and 289 (85.8%) were BCR-ABLIS (International Scale, IS) ≤1% by RQ-PCR, compared to 9.0 (261/290) were BCR-ABLIS ≤1% among 290 samples with FISH-CCyR. There was no significant difference in the median value of BCR-ABLIS between samples in CBA-CCyR and FISH-CCyR (0.21%
6. Clinical analysis of myeloid neoplasms with t (3;21) (q26;q22)
Ye LI ; Qing LIU ; Zheng WANG ; Yazhen QIN ; Hui DANG ; Yan SHI ; Qi HE ; Qian JIANG ; Hao JIANG ; Yueyun LAI
Chinese Journal of Hematology 2019;40(3):195-199
Objective:
To analyze the characteristics of myeloid neoplasms with t (3;21) (q26;q22) .
Methods:
Clinical data of patients with t (3; 21) (q26; q22) , diagnosed as hematologic malignancies in Peking University people's hospital from January 2011 to March 2018, were collected retrospectively. 19 patients in our hospital and forty-eight patients bearing t (3;21) (q26;q22) with detailed survival data reported in literature were summarized. Kaplan- Meier method was used for survival analysis.
Results:
Among 19 patients, including 15 males and 4 females with a median age of 36 years (22-68 years) , 4 cases was diagnosed as de novo acute myeloid leukemia (AML) , 4 as myelodysplastic syndromes (MDS) , 3 as MDS-AML and 8 as chronic myelogenous leukemia (CML) in myeloid blast transformation. All of the 19 patients were detected to have t (3;21) (q26;q22) by G-banding technique and 13 carried additional cytogenetic aberrations. 9 of the 19 patients were detected for positive AML1-MDS1 fusion genes. In the 9 patients with detailed follow-up data, 6 patients received chemotherapy and only 2 achieved complete remission (CR) while 4 with no response. During the follow-up period, 8 patients died and the median overall survival (OS) was 6 months (4.5 to 22 months) . Survival analysis of the present 9 patients together with the literature data showed that the prognosis was poor and the median OS was 7 months. In particular, AML/t-AML had the worst prognosis. Hematopoietic stem cell transplantation (HSCT) could significantly improve survival, the median OS in HSCT group and non-HSCT group were 20.9 and 4.7 months respectively (
7.Transformation from promyelocytic leukemia with t (15; 17) ( q22; q21) to acute monocytic leukemia with t (11; 17) (q23; q21) in a case.
Zheng WANG ; Ye LI ; Hui DANG ; Yan SHI ; Qi HE ; Lin FENG ; Li BAO ; Yazhen QIN ; Yanrong LIU ; Xiaojun HUANG ; Yueyun LAI
Chinese Journal of Medical Genetics 2018;35(2):276-279
OBJECTIVETo report on a case of therapy-related acute monocytic leukemia(t-AML) with t(11;17) (q23;q21)/MLL-AF17q after successful treatment for acute promyelocytic leukemia(APL) with t(15;17) (q22;q21)/PML-RARα.
METHODSA MICM method (bone marrow morphology(M), immunophenotype(I), cytogenetics(C), and molecular biology(M)) was used for the diagnosis and classification of the disease at the time of onset and transformation.
RESULTSThe patient was initially identified with typical morphology and immunophenotype of APL. She has carried t(15;17)(q22;q21) and PML-RARα fusion gene but was without t(11;17)(q23;q21) or MLL gene abnormalities. After 13 months of successful treatment, she has transformed to AML with typical morphology and immunophenotype. t(11;17)(q23;q21) and MLL-AF17q fusion gene were detected in her bone marrow sample, while no PLZF-RARα fusion gene was detected by real-time quantitative reverse-transcription PCR(RQ-PCR) and fluorescence in situ hybridization(FISH).
CONCLUSIONt-AML is a serious complication after successful treatment of APL. t(11;17)(q23;q21) is not specific for the diagnosis of variant APL and can also be detected in t-AML. RQ-PCR and FISH are essential for the diagnosis of such patients.
Chromosomes, Human, Pair 11 ; Chromosomes, Human, Pair 15 ; Chromosomes, Human, Pair 17 ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Leukemia, Monocytic, Acute ; genetics ; Leukemia, Promyelocytic, Acute ; genetics ; Middle Aged ; Neoplasms, Second Primary ; genetics
8.Effect of modified citrus pectin on synovial fibroblasts
Yazhen CHEN ; Danning SU ; Jianuo ZHENG ; Jiayue HE ; Ruiping DUAN ; Bo DU ; Xuemin LI ; Lingrong LIU
International Journal of Biomedical Engineering 2023;46(2):97-103
Objective:To study the effects of modified citrus pectin (MCP) on the viability and gene expressions of synovial fibroblasts (SF) as well as SF treated by galectin-3 (Gal-3).Methods:Rabbit SF was isolated and cultured in vitro. Then SF was treated with different concentrations of MCP (0, 250, 500, and 750 mg/L). In addition, SF was further treated with the same different concentrations of MCP after treatment with 10 μg/ml Gal-3 for 24 h. The viability of SF was detected by CCK-8 on the first, third, and fifth day after treatment. The mRNA expression of transforming growth factor-β1 (TGF-β1), type I collagen (COL1A2), and Gal-3 in SF was detected by real-time quantitative PCR. The synthesis of type I collagen in SF was investigated by immunofluorescence staining. Results:MCP, especially at a concentration of 500 mg/L can inhibit the proliferation of SF significantly (all P < 0.05) on the first, third, and fifth day after treatment. Compared with the control group, MCP at different concentrations induced different gene expression profiles. In particular, MCP at high concentrations can upregulate the expression of TGF-β1, COL1A2 and Gal-3 in SF. However, MCP shows no significant effect on the synthesis of type I collagen in SF. MCP can down-regulate the expression of TGF-β1, COL1A2, and significantly reduce the synthesis of type I collagen in SF after Gal-3 treatment. Particularly, the effect of MCP at a concentration of 500 mg/L on inhibiting the expression of TGF-β1, COL1A2, and Gal-3 in SF is significant. Conclusions:MCP can inhibit the excessive proliferation of SF and regulate gene expression in SF.
9.Analysis of the characteristics of primary acute myeloid leukemia with 11q23/KMT2A rearrangements in ninety patients.
Ye LI ; Yanlin WANG ; Zheng WANG ; Lin FENG ; Lu GAO ; Yan SHI ; Hui DANG ; Qi HE ; Yazhen QIN ; Qian JIANG ; Hao JIANG ; Xiaojun HUANG ; Yueyun LAI
Chinese Journal of Medical Genetics 2023;40(12):1472-1477
OBJECTIVE:
To investigate the clinical and prognostic characteristics of primary acute myeloid leukemia (AML) with 11q23/KMT2A rearrangements.
METHODS:
Clinical data of 90 patients with primary AML and 11q23/KMT2A rearrangements were analyzed retrospectively.
RESULTS:
By karyotyping analysis, 80 of the 90 patients had translocations involving 11q23/KMT2A, with t(9;11)(p22;q23), t(6;11)(q27;q23), t(10;11)(p12;q23) and t(11;19)(q23;p13) being the most common ones, while 10 cases were found to have non-translocation abnormalities. The overall complete remission (CR) rate was 75.6%, and patients with t(6;11) had lower CR rate compared with non-t(6;11) patients (47.1% vs. 82.2%, P = 0.005). After a median follow-up of 24.5 months, the patients receiving allo-hematopoietic stem cell transplantation (allo-HSCT) had significantly higher 3-year overall survival (OS) (80.3% vs. 16.6%, P < 0.001) and 3-year event-free survival (EFS) (73.5% vs. 16.3%, P < 0.001) compared with non-transplant patients. Patients with t(6;11) had the lowest 3-year OS (11.8% vs. 56.0%, P < 0.001) and 3-year EFS (5.9% vs. 53.8%, P < 0.001) compared with other type of abnormalities. No significant difference was noted in the survival between patients with t(9;11) and non-t(9;11) regardless whether they had received HSCT.
CONCLUSION
The clinical characteristics of primary AML with 11q23/KMT2A rearrangements are heterogeneous. Patients did not receive HSCT had poorer survival, particularly with the presence of t(6;11). Allo-HSCT could significantly improve the survival of such patients.
Humans
;
Retrospective Studies
;
Leukemia, Myeloid, Acute/therapy*
;
Translocation, Genetic
;
Gene Rearrangement
;
Prognosis