1.Effect of Cyr61 on Imatinib Resistance in Chronic Myeloid Leukemia and Its Mechanism.
Yan-Fang SONG ; Li LUO ; Peng-Chong SHI ; Zhao-Zhong LI ; Tai-Gang ZHANG ; Ying-Ping CAO ; Xian-Jin ZHU
Journal of Experimental Hematology 2023;31(1):1-7
OBJECTIVE:
To investigate the effect of Cyr61 on imatinib (IM) resistance in chronic myeloid leukemia (CML) and its mechanism.
METHODS:
Cyr61 level in cell culture supernatant was determined by enzyme-linked immunosorbent assay. The expression of Cyr61 and Bcl-xL were measured by real-time PCR and Western blot. Cell apoptosis was analyzed using an Annexin V-APC Kit. Expression of signal pathways related proteins was determined by Western blot.
RESULTS:
The level of Cyr61 obviously increased in K562G cells (IM resistance to CML cell line K562). Down-regulating the expression of Cyr61 decreased the resistance of K562G cells to IM and promoted IM induced apoptosis. In CML mouse model, down-regulating the expression of Cyr61 could increase the sensitivity of K562G cells to IM. The mechanism studies showed that Cyr61 mediated IM resistance in CML cells was related to the regulation of ERK1/2 pathways and apoptosis related molecule Bcl-xL by Cyr61.
CONCLUSION
Cyr61 plays an important role in promoting IM resistance of CML cells. Targeting Cyr61 or its related effectors pathways may be one of the ways to overcome IM resistance of CML cells.
Animals
;
Humans
;
Mice
;
Apoptosis
;
Drug Resistance, Neoplasm
;
Imatinib Mesylate/pharmacology*
;
K562 Cells
;
Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism*
;
Signal Transduction
2.Clinical Characteristics of Children with Hemophagocytic Syndrome with Different EB Virus DNA Loads.
Jiao-Jiao HUANG ; Nan-Du LUO ; Zuo-Chen DU ; Jia-Hong YAN ; Jin-Hua MA ; Xiu-Li CAO ; Zhi-Xu HE ; Pei HUANG ; Yan CHEN
Journal of Experimental Hematology 2023;31(1):261-267
OBJECTIVE:
To analyze the clinical characteristics of hemophagocytic syndrome (HLH) children with different EB virus (EBV) DNA loads, and to explore the relationship between differential indicators and prognosis.
METHODS:
Clinical data of 73 children with HLH treated in our hospital from January 2015 to April 2022 were collected. According to EBV DNA loads, the children were divided into negative group (≤5×102 copies/ml), low load group (>5×102-<5×105 copies/ml) and high load group (≥5×105copies/ml). The clinical symptoms and laboratory indexes of the three groups were compared, and the ROC curve was used to determine the best cut-off value of the different indexes. Cox regression model was used to analyze the independent risk factors affecting the prognosis of children, and to analyze the survival of children in each group.
RESULTS:
The proportion of female children, the swelling rate of liver and spleen lymph nodes and the involvement rate of blood, liver, circulation and central nervous system in the high load group were higher than those in the negative group. The incidence of disseminated intravascular coagulation(DIC) and central nervous system(CNS) involvement in the high load group were higher than those in the low load group. The liver swelling rate and circulatory system involvement rate in the low load group were higher than those in the negative group(P<0.05). PLT counts in the high load group were significantly lower than those in the negative group, and the levels of GGT, TBIL, CK-MB, LDH, TG, SF, and organ involvement were significantly higher than those in the negative group. The levels of CK, LDH, SF and the number of organ involvement in the high load group were significantly higher than those in the low load group. The levels of GGT and TBIL in low load group were significantly higher than those in negative group. In terms of treatment, the proportion of blood purification therapy in the high and low load group was significantly higher than that in the negative group(P<0.01). ROC curve analysis showed that the best cut-off values of PLT, LDH, TG and SF were 49.5, 1139, 3.12 and 1812, respectively. The appellate laboratory indicators were dichotomized according to the cut-off value, and the differential clinical symptoms were included in the Cox regression model. Univariate analysis showed that LDH>1139 U/L, SF>1812 μg/L, dysfunction of central nervous system, number of organ damage, DIC and no blood purification therapy were the risk factors affecting the prognosis of children (P<0.05); Multivariate analysis shows that PLT≤49.5×109/L and dysfunction of central nervous system were risk factors affecting the prognosis of children (P<0.05). Survival analysis showed that there was no significant difference in the survival rate among the three groups.
CONCLUSION
The incidence of adverse prognostic factors in children with HLH in the EBV-DNA high load group is higher, and there is no significant difference in the survival rate of the three groups after blood purification therapy. Therefore, early identification and application of blood purification therapy is of great significance for children with HLH in the high load group.
Humans
;
Child
;
Female
;
Lymphohistiocytosis, Hemophagocytic
;
Retrospective Studies
;
Risk Factors
;
DNA
;
Prognosis
3.Correlation Analysis between Cerebrospinal Fluid Status and Prognosis in Childhood with Acute Lymphoblastic Leukemia by Flow Cytometry.
Li-Li DING ; Hao XIONG ; Li YANG ; Yan CHEN ; Yu DU ; Wen-Jie LU ; Shan-Shan QI ; Zhi CHEN ; Ming SUN ; Lin-Lin LUO
Journal of Experimental Hematology 2023;31(3):654-658
OBJECTIVE:
To study the cerebrospinal fluid (CSF) status and prognosis value in patients with newly diagnosed acute lymphoblastic leukemia (ALL) by flow cytometry (FCM).
METHODS:
The clinical features of the 75 newly diagnosed ALL patients from September 2020 to December 2021 in our centre were retrospective analyzed, as well as the bone marrow (BM) and CSF minimal residual disease (MRD) data, and the CSF conventional cytology data. Central nervous system infiltration(CNSI) positive was as CSF MRD positive by FCM or leukemia cells detected by conventional cytology. The status of CSF were compared and analyzed by FCM and conventional cytology, the clinical features and the prognosis value of different CNSI status in these patients were analyzed.
RESULTS:
Among 75 newly diagnosed ALL, 16 cases (21%) with CNSI positive (CNSI+) were detected by FCM, while only 2 positive cases (3%) were detected by conventional cytology. The CNSI+ rate detected by FCM was significantly higher than conventional cytology(P<0.05). Compared with CNSI- ALL patients, the median age of CNSI+ ALL patients was significantly younger, and the median platelet count was significantly lower, the difference was statistically significant (P<0.05). Up to follow-up time (August 31, 2022), four ALL patients were died, including 3 patients were CNSI- and 1 patient was CNSI+. Furthermore, three cases were primary disease relapse, including 1 case was CNSI+. There was no significant difference in overall survival (OS) rate and relapse-free survival (RFS) rate of the patients with different CNSI status.
CONCLUSION
Compared with conventional cytology, FCM is a more sensitive assay to evaluate the central nervous system status in ALL patients. After active treatment, there was no significant difference in OS and RFS between patients with different CNSI status at diagnosis.
Humans
;
Retrospective Studies
;
Flow Cytometry
;
Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy*
;
Prognosis
;
Bone Marrow
;
Neoplasm, Residual
;
Recurrence
4.Investigation and analysis of airborne allergenic pollen in 4 districts and 5 counties of Hohhot City.
Hui Yu NING ; Hui Jiao CAI ; Ting Ting MA ; Chang E FAN ; Dong Dong WU ; Feng Ying GAO ; Fan KONG ; Fu Jun ZHANG ; Rong WANG ; Hui Hui GUO ; Run Lan MA ; Cai Ying ZHENG ; Bo HAO ; Hong Tian WANG ; Jun Jing ZHANG ; Luo ZHANG ; Xue Yan WANG
Chinese Journal of Preventive Medicine 2023;57(9):1364-1372
Objective: To investigate the species, concentration and seasonal trends of main airborne allergenic pollen in 4 districts and 5 counties of Hohhot City. Methods: The Department of allergy, Beijing Shijitan Hospital Affiliated to Capital Medical University conducted a cross-sectional study about monitoring the airborne allergenic pollen from August 1, 2021 to July 31, 2022 by the gravitational method in 4 districts and 5 counties of Hohhot City, which include Yuquan District, Xincheng District, Huimin District, Saihan District, Tuoketuo County, Helingeer County, Tumotezuoqi County, Wuchuan County and Qingshuihe County. Daily pollens were counted and identified by optical microscopy, and the data were analyzed. Results: The airborne allergenic pollen was collected every month all year round in 4 districts and 5 counties of Hohhot city. Through the whole year of the total quantity of pollens ranged from 24 850 to 50 154 grains per 1 000 mm2 and two peaks of pollen concentration in air were observed,which happened in spring (from March to May) and in summer and autumn (from July to September). In spring, the main pollens were tree pollens, which principally distributed in Populus pollen (18.29%), Ulmus pollen (8.36%), Pinus pollen (6.20%), Cupressaceae pollen (5.23%), Betulaceae pollen (2.73%), Salix pollen (1.80%) and Quercus pollen (1.16%). In summer and autumn, the main pollens were weed pollens, which mainly included Artemisia pollen (42.73%), Chenopodiaceae pollen or Amaranthaceae pollen (7.46%), Poaceae pollen (2.26%), Humulus pollen or Cannabis pollen (0.60%). Conclusion: There were two peaks of main airborne allergenic pollen in 4 districts and 5 counties of Hohhot City. In the spring peak of pollen, the main airborne pollens were tree pollens. In the summer and autumn peak of pollen, the main airborne pollens were weed pollens. The Artemisia pollen was the most major airborne pollen in this area.
Humans
;
Cross-Sectional Studies
;
Pollen
;
Hospitals
5.Investigation and analysis of airborne allergenic pollen in 4 districts and 5 counties of Hohhot City.
Hui Yu NING ; Hui Jiao CAI ; Ting Ting MA ; Chang E FAN ; Dong Dong WU ; Feng Ying GAO ; Fan KONG ; Fu Jun ZHANG ; Rong WANG ; Hui Hui GUO ; Run Lan MA ; Cai Ying ZHENG ; Bo HAO ; Hong Tian WANG ; Jun Jing ZHANG ; Luo ZHANG ; Xue Yan WANG
Chinese Journal of Preventive Medicine 2023;57(9):1364-1372
Objective: To investigate the species, concentration and seasonal trends of main airborne allergenic pollen in 4 districts and 5 counties of Hohhot City. Methods: The Department of allergy, Beijing Shijitan Hospital Affiliated to Capital Medical University conducted a cross-sectional study about monitoring the airborne allergenic pollen from August 1, 2021 to July 31, 2022 by the gravitational method in 4 districts and 5 counties of Hohhot City, which include Yuquan District, Xincheng District, Huimin District, Saihan District, Tuoketuo County, Helingeer County, Tumotezuoqi County, Wuchuan County and Qingshuihe County. Daily pollens were counted and identified by optical microscopy, and the data were analyzed. Results: The airborne allergenic pollen was collected every month all year round in 4 districts and 5 counties of Hohhot city. Through the whole year of the total quantity of pollens ranged from 24 850 to 50 154 grains per 1 000 mm2 and two peaks of pollen concentration in air were observed,which happened in spring (from March to May) and in summer and autumn (from July to September). In spring, the main pollens were tree pollens, which principally distributed in Populus pollen (18.29%), Ulmus pollen (8.36%), Pinus pollen (6.20%), Cupressaceae pollen (5.23%), Betulaceae pollen (2.73%), Salix pollen (1.80%) and Quercus pollen (1.16%). In summer and autumn, the main pollens were weed pollens, which mainly included Artemisia pollen (42.73%), Chenopodiaceae pollen or Amaranthaceae pollen (7.46%), Poaceae pollen (2.26%), Humulus pollen or Cannabis pollen (0.60%). Conclusion: There were two peaks of main airborne allergenic pollen in 4 districts and 5 counties of Hohhot City. In the spring peak of pollen, the main airborne pollens were tree pollens. In the summer and autumn peak of pollen, the main airborne pollens were weed pollens. The Artemisia pollen was the most major airborne pollen in this area.
Humans
;
Cross-Sectional Studies
;
Pollen
;
Hospitals
6.Dihydroartemisinin Induces Autophagic Cell Death in Acute Myeloid Leukemia Cells through Oxidative Stress.
Wei PAN ; Yan SHEN ; Bo LUO ; Yu CAO
Journal of Experimental Hematology 2022;30(4):1011-1017
OBJECTIVE:
To investigate the potential value and its mechanism of dihydroartemisinin (DHA) in the treatment of acute myeloid leukemia (AML).
METHODS:
The effect of DHA on the viability of AML cells was detected by CCK-8 assay. The effect of DHA on intracellular oxidation-reduction state was detected by fluorescence probe staining and flow cytometry. Western blot, adenovirus transfection, and laser confocal analysis were used to analyze the effect of DHA on autophagy. The small molecule inhibitors were used to further elucidate the possible mechanism of DHA-induced AML cell death.
RESULTS:
DHA could inhibit the viability of HL-60 and Kasumi-1 cell lines, and significantly increase the level of intracellular oxidative stress. When treated with 10 μmol/L DHA, reactive oxygen species (ROS) in HL-60 cells and Kasumi-1 cells was increased to 2.6 times and 2.0 times, respectively. In addition, the expression of autophagy-related proteins were up-regulated in DHA-treated AML cells, together with the increase of intracellular autophagy flux and activation of autophagy. Furthermore, autophagy inhibitors reduced DHA-induced cell death, and inhibited the level of oxidative stress by scavenging intracellular free radicals, thus inhibiting autophagy and restoring cell viability.
CONCLUSION
DHA can activate autophagic cell death of AML by inducing oxidative stress.
Apoptosis
;
Artemisinins/pharmacology*
;
Autophagic Cell Death
;
Autophagy
;
Humans
;
Leukemia, Myeloid, Acute
;
Oxidative Stress
7.Clinical Significance of Truncated Mutant ΔJBP of TET2 Gene in Patients with Acute Myeloid Leukemia.
Yu-Chao YANG ; Ting XIA ; Ming LUO ; Wen-Zheng GUO ; Ling-Li ZHANG ; Xiu-Hua CHEN ; Zhi-Fang XU ; Hong-Wei WANG ; Yan-Hong TAN
Journal of Experimental Hematology 2021;29(4):1011-1018
OBJECTIVE:
To the clinical characteristics and prognostic value of the patients with complete deletion of TET_JBP domain (ΔJBP) in TET2 acute myeloid leukemia (AML).
METHODS:
Next Generation Sequencing technology was used to determine the mutations of 34 AML-related genes (including TET2 gene). The I-TASSER tool was used to predict the tertiary structure of the full-length TET2 protein and TET_JBP structure deletion.
RESULTS:
Among 38 AML patients with TET2 mutations, 22(57.9%) showed truncation mutations, of which 16 (72.7%) produced TET2ΔJBP truncation mutants. Protein structure prediction showed that the deletion of TET_JBP domain lead to the significant changes of tertiary structure in TET2 protein. Compared with the patients in non-ΔJBP group, the age of patients in ΔJBP group were older (63 vs 54 years old, P=0.047), and the occurrence rate of CEBPA double mutation (CEBPA
CONCLUSION
AML patients with TET2ΔJBP truncation mutant shows lower CR rate, shorter EFS and OS after induction chemotherapy, which may be related to the poor prognosis, and co-mutation with CEBPA
DNA-Binding Proteins/genetics*
;
Humans
;
Induction Chemotherapy
;
Leukemia, Myeloid, Acute/genetics*
;
Middle Aged
;
Mutation
;
Prognosis
;
Proto-Oncogene Proteins/genetics*
;
Remission Induction
8.Effects of Long Non-coding RNA-TUC338 on the Migration and Proliferation of Lymphoma Cells via PI3K/AKT Signaling Pathway.
Zhen-Wei JIA ; Yan LI ; Xiao-Yang KONG ; Hong-Bo ZHAO ; Zhi-Feng YANG ; Jing-Wei YE ; Gui-Rong CUI ; Jian-Min LUO
Journal of Experimental Hematology 2021;29(2):494-499
OBJECTIVE:
To investigate the effect of long non-coding RNA-TUC338 on the proliferation and migration of lymphoma cells.
METHODS:
The expression of TUC338 in different lymphoma cells was detected by fluorescence quantitative PCR, cell proliferation by sulforhodamine B (SRB) assay, migration of lymphoma cells by transwell assay, and protein expression in PI3K/AKT signaling pathway by Western blot.
RESULTS:
The expression levels of TUC338 in lymphoma cells Daudi, U937, BC-3, and Raji significantly increased in comparison with human normal T lymphocytes H9 (t=13.277, 10.103, 16.200, and 26.687, P=0.002, 0.005, 0.001, and 0.000). Compared with NC-siRNA group, the number of cells crossing the chamber of TUC338-siRNA group was significantly reduced (t=30.508, P=0.000), the protein expression levels of p-PI3K and p-AKT significantly decreased (t=16.872 and 18.371, P=0.000 and 0.000), and OD
CONCLUSION
The expression of TUC338 significantly increases in lymphoma cells, and silence of TUC338 effectively inhibits the activation of PI3K/AKT signaling pathway, thereby inhibiting the proliferation and migration of lymphoma cells, which has a potential application value in diagnosis and treatment of lymphoma.
Cell Line, Tumor
;
Cell Movement
;
Cell Proliferation
;
Humans
;
Phosphatidylinositol 3-Kinases/metabolism*
;
Proto-Oncogene Proteins c-akt/metabolism*
;
RNA, Long Noncoding/genetics*
;
Signal Transduction
9.Exploring the Mechanism of Paclitaxel Inhibiting T-cell Lymphoma based on High-throughput Sequencing and Public Databases.
Si-Zhu LI ; Yi-Bin YAO ; Zhong-Yuan TANG ; Ze-Yan SHI ; Ze-Guang WU ; Bin LUO ; Zhi-Gang PENG
Journal of Experimental Hematology 2021;29(3):741-750
OBJECTIVE:
To analyze gene expression profile of T cell lymphoma Jurkat cell line treated with paclitaxel by computational biology based on next generation sequencing and to explore the possible molecular mechanism of paclitaxel resistance to T cell lymphoma at gene level.
METHODS:
IC50 of paclitaxel on Jurkat cell line was determined by CCK-8 assay. Gene expression profile of Jurkat cells treated with paclitaxel was acquired by next generation sequencing technology. Gene microarray data related to human T cell lymphoma were screened from Gene Expression Omnibus (GEO) database (including 720 cases of T cell lymphoma and 153 cases of normal tissues). Combined with the sequencing data, differential expression genes (DEGs) were intersected and screened. DAVID database was used for enrichment analysis of GO function and KEGG pathway to determine and visualize functional entries of DEGs, and protein-protein interactions network of DEGs was drawn. The levels of gene expression were detected and verified by RT-qPCR.
RESULTS:
CCK-8 results showed that the proliferation of Jurkat cells was inhibited by paclitaxel depended on the concentration apparently. Treated by paclitaxel for 48 h, P<0.05 and |log2(FC)|≥1 were used as filter criteria on the results of RNA Sequencing (RNA-Seq) and GeoChip, 351 DEGs were found from Jurkat cells, including 323 up-regulated genes and 28 down-regulated genes. The GO functional annotation and KEGG pathway enrichment analysis showed that the role of paclitaxel was mainly concentrated in protein heterodimerization activity, nucleosome assembly and transcriptional dysregulation in cancer, etc. The results of RT-qPCR were consistent with those of the sequencing analysis, which verified the reliability of this sequencing.
CONCLUSION
Paclitaxel can affect the proliferation and apoptosis of T-cell lymphoma by up-regulating JUN gene, orphan nuclear receptor NR4A family genes and histone family genes.
Computational Biology
;
Gene Expression Profiling
;
Gene Expression Regulation, Neoplastic
;
High-Throughput Nucleotide Sequencing
;
Humans
;
Lymphoma, T-Cell
;
Paclitaxel
;
Reproducibility of Results
10.Methodological Evaluation of Microarray in the Detection of α-Thalassemia.
Peng-Fei CAI ; Liu-Qun QIN ; Shi-Qiang LUO ; Li-Zhu CHEN ; Qing-Yan ZHONG ; Jing-Ren WANG ; Qiu-Hua WANG ; Jun HUANG ; Ti-Zhen YAN
Journal of Experimental Hematology 2021;29(6):1907-1910
OBJECTIVE:
To proceed the clinical evaluation of DNA microarray for thalassemia gene detection.
METHODS:
Peripheral blood samples of 166 thalassemia gene test subjects were collected and tested for thalassemia genes by microarray chip method and Gap-PCR method combined with PCR-reverse dot blot hybridization method according to double-blind control test. The specificity, sensitivity, positive predictive value, negative predictive value, and total coincidence rate of the microarray chip method were evaluated. When the two methods were inconsistent, multiplex ligation dependent probe amplification (MLPA) was used to verify the deletional α-thalassemia.
RESULTS:
Compared with Gap-PCR method, specificity, sensitivity, positive predictive value, negative predictive value, Youden index, and total coincidence rate of microarray chip method was 100% (70/70), 96.88% (93/96), 100% (93/93), 95.89% (70/73), 0.969, and 97.59% (162/166), respectively, while compared with PCR-reverse dot blot hybridization method was 100% (125/125), 100% (41/41), 100% (41/41), 100% (125/125), 1, and 100% (166/166), respectively.
CONCLUSION
The microarray chip method for α-thalassemia gene detection shows the advantages of high specificity, sensitivity, and throughput.
Genetic Testing
;
Humans
;
Multiplex Polymerase Chain Reaction
;
Oligonucleotide Array Sequence Analysis
;
alpha-Thalassemia/genetics*

Result Analysis
Print
Save
E-mail