4.Effect of Bmi-1 Expression on Chemotherapy Sensitivity in THP-1 Cells.
Si-Cong DONG ; Ru-Nan JING ; Hao PEI ; Fan LIU ; Bao-Xia ZHAO ; Xiu-Xiang MENG
Journal of Experimental Hematology 2021;29(2):363-368
OBJECTIVE:
To investigate the effect of Bmi-1 expression on the chemosensitivity of THP-1 cells and its relative mechanism.
METHODS:
The pGenesil-2-Bmi-1 1 siRNA, p-MSCV-Bmi-1 plasmid was transfected into THP-1 cells to reduce or increase the expression of Bmi-1. The expression of Bmi-1 mRNA and protein was verified by PCR and Western blot. The effect of camptothecin (CPT) on the proliferation and chemosensitivity of THP-1 cells affected by Bmi-1 gene were detected by MTT assay. The expression of DNA double-strand breaks marker-γ-H2AX was detected by immunofluorescence assay. Mitochondrial membrane potential and apoptosis were observed by flow cytometry. The expression of Cytochrome C, Caspase 3, Bax and BCL-2 was detected by Western blot.
RESULTS:
Silencing Bmi-1 could inhibit proliferation and enhance the sensitivity of THP-1 cells to CPT, while overexpressed Bmi-1 could promote the cell proliferation and attenucate sensitivity of THP-1 cells to CPT. Silencing Bmi-1 could enhance CPT-induced DNA double-strand breaks, decrease mitochondrial membrane potential and promote CPT-induced apoptosis. While increasing Bmi-1 gene expression could attenuate CPT-induced DNA double-strand breaks, enhamce mitochondrial membrane potential and significantly reduce CPT-induced apoptosis of cells.
CONCLUSION
Bmi-1 expression could influence the sensitivity of THP-1 cells to CPT, and its relative mechanism may relate to DNA double-strand breaks and endogenous apoptotic pathways.
Apoptosis
;
Camptothecin/pharmacology*
;
Cell Line, Tumor
;
Cell Proliferation
;
THP-1 Cells
5.Clinical Characteristics and Prognosis of Patients with Primary Bone Diffuse Large B-Cell Lymphoma.
You-Fan FENG ; Xiao-Fang WEI ; Qi-Ke ZHANG ; Li ZHAO ; Xiao-Qin LIANG ; Yuan FU ; Xiu-Juan HUANG ; Qing-Fen LI
Journal of Experimental Hematology 2021;29(5):1517-1521
METHODS:
The clinical data of 15 patients with primary diffuse large B-cell lymphoma treated in our hospital from January 2013 to December 2020 were collected, the clinical data and prognosis of the patients were analyzed retrospectively.
RESULTS:
The median age of the 15 patients was 59 (19-89) years old; among the patients, 7 were males and 8 were females, ostealgia was the initial symptom. The pathological types of the 15 patients were diffuse large B-cell lymphoma (DLBCL), 5 cases of Has type GCB subtype (5/15), and 10 cases of Non-GCB subtype (10/15). After 15 patients were diagnosed, 11 patients (11/15) received chemotherapy, 3 patients (3/15) received surgery, and 1 patient was untreated (1/15), median chemotherapy courses was 5 (1-9). 8 patients have achieved complete remission (8/15), 3 patients achieved partial remission (3/15), and 1 patient achieved stable disease (1/15), 1 patient was lost to follow-up (1/15), 1 patient was untreated (1/15), and 1 patient was progression of disease (1/15). Age, pathological subtype, sex, stage, β2-MG level, LDH level, and the using of rituximab were not correlated with the complete remission rate of the patients(P>0.05), while the IPI score was correlated with the recent complete remission rate (P<0.05). The median follow-up time was 19 (1-38) months, 10 patients survived, in which 6 cases were still in complete remission, and the median time to progression-free survival was 15 (1-38) months.
CONCLUSION
The first symptom of primary bone diffuse large B-cell lymphoma is bone pain, the main pathological subtype is Non-GCB, the optimal treatment is combined chemotherapy, and the IPI score is related to the prognosis of the treatment.
Aged
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Aged, 80 and over
;
Female
;
Humans
;
Lymphoma, Large B-Cell, Diffuse
;
Male
;
Middle Aged
;
Prognosis
;
Remission Induction
;
Retrospective Studies
;
Rituximab
6.Influence of FLT3-ITD Mutation and ITD Length on the Outcome on Patients with Acute Myeloid Leukemia.
Fang CHEN ; Xue-Jie JIANG ; Chang-Xin YIN ; Qing-Xiu ZHONG ; Ling JIANG ; Guo-Pan YU ; Jing SUN ; Fan-Yi MENG
Journal of Experimental Hematology 2018;26(3):678-683
OBJECTIVETo explore the influence of FLT3-ITD mutation and ITD length on the overall survival (OS) and relapse free survival(RFS) in patients with non-M3 acute myeloid leukemia.
METHODSClinical features and therapeutic effect were retrospectively analyzed in 75 AML patients with FLT3-ITD mutation and 76 FLT3-ITD AML patients with a normal karotype from June 2011 to April 2016. Genomic DNA was amplified by PCR, and FLT3-ITD mutation length was analyzed by DNA sequencing in 40 patients.
RESULTSAML patients with FLT3-ITD mutation had higher WBC count and the ratio of BM blast cells at initial diagnosis was also higher than those in AML patients without FLT3-ITD mutation (95.13 vs 10.85)(P<0.01); 72% vs 59%(P<0.01). The CR rates in AML patients with FLT3-ITD mutation less than those in AML patients without FLT3-ITD mutation(70.42% vs 94.7%)(P<0.01). OS (P<0.01) and RFS (P<0.01) were significantly increased in patients with AML who received allo-HSCT as compared with the patients who received consolidation chemotherapy and similar to AML patients without FLT3-ITD mutation who received HSCT. Patients with maintenance sorafenib after HSCT had longer OS (P<0.05) and RFS (P<0.05) than controls. ITDs exceeding 60 bp in length were associated with decreasing OS as compared with shorter ITD in AML patients with FLT3-ITD mutation (P<0.05). OS and RFS were similar among the 2 groups receiving consolidation chemotherapy. Besides, the patients with allo-HSCT had shorter ITDs and longer OS than ITDs exceeding 60 bp (P<0.05) and similar to AML patients without FLT3-ITD mutation.
CONCLUSIONAML patients with FLT3-ITD mutation has poorer outcome, among which the prognosis was worse in patients with ITD exceeding 60 bp, and the chemotherapy alone can not improve the prognosis of FLT3-ITD. Allo-HSCT is an effective treatment for AML patients with FLT3-ITD mutation; Sorafenib appears to be an effective maintenance therapy after allo-HSCT in FLT3-ITD AML.
Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myeloid, Acute ; Mutation ; Oncogene Proteins, Fusion ; Prognosis ; Retrospective Studies ; fms-Like Tyrosine Kinase 3
7.The Influence of Serum Homocysteine Level to the Prognosis of Newly Diagnosed Multiple Myeloma Patients and Analysis of Related Factors.
Yuan FU ; Xiao-Fang WEI ; You-Fan FENG ; Fei LIU ; Qiao-Lin CHEN ; Yang-Yang ZHAO ; Wen-Jie ZHANG ; Ting MA ; Xiu-Juan HUANG ; Yang CHEN ; Qing-Fen LI ; Qi-Ke ZHANG
Journal of Experimental Hematology 2021;29(2):530-534
OBJECTIVE:
To analyze the influence of serum homocysteine (Hcy) levels to the prognosis of newly diagnosed multiple myeloma (MM) patients, and to explore related factors affecting the prognosis of the patients.
METHODS:
The clinical pathological data of 180 newly diagnosed MM patients treated in our hospital from March 2013 to February 2015 were collected, and the patients were divided into high and low Hcy groups based on the median Hcy. The survival curves of the patients in the two groups were drawn to compare the differences of the survival; univariate and multivariate survival analysis was used to observe the influence of serum cysteine to the prognosis of newly diagnosed MM patients; the clinicopathological data of the patients with high and low Hcy in the two groups was compared, Pearson test was used to further analyzes the relationship between Hcy and different factors, and explores the related factors of Hcy affecting the prognosis of the patients.
RESULTS:
The median survival times of patients in the high and low Hcy groups were 32 (5-59) and 41 (7-71) months, respectively. The 3-year survival rate of the patients in high Hcy group was significantly lower than those in low Hcy group, and the difference shows statistically significant (P<0.05). The results of univariate survival analysis showed that the OS of newly diagnosed MM patients whom with advanced age, high bone disease grade, high-level bone marrow plasma cell count, LDH, C-reactive protein, Cr, β
CONCLUSION
Serum Hcy level has a correlation trend with the survival of newly diagnosed MM, which is affected by factors such as Hb.
Bone Marrow Cells
;
Homocysteine
;
Humans
;
Multiple Myeloma
;
Prognosis
;
Risk Factors
8.Effect of Signal Transduction Pathway Gene Mutations on the One- course Induced Remission Rate and Analysis of Clinical Characteristics in Patients with CBF-AML.
Li-Fang FAN ; Jing XU ; Xiu-Hua CHEN ; Ting-Ting TIAN ; Juan XIE ; Jin-Jun HU ; Zhi-Ping GUO ; Yan-Hong TAN ; Zhi-Fang XU ; Fang-Gang REN ; Yao-Fang ZHANG ; Ming LUO ; Wei-Xiao REN ; Hong-Wei WANG
Journal of Experimental Hematology 2020;28(3):781-788
OBJECTIVE:
To investigate the effect of other gene mutations outside the fusion gene on the first complete remission (CR) induced by one course of induction chemotherapy in patients with core binding factor-associated acute myeloid leukemia (CBF-AML).
METHODS:
DNA was extracted from bone marrow or peripheral blood samples of newly diagnosed CBF-AML patients admitted to the Hematology Department of the Second Hospital of Shanxi Medical University from January 2015 to January 2019. Next-generation sequencing was used for detection of 34 kinds of hematologic malignancy-related gene mutations in patients with CBF-AML, the effect of related gene mutations on the first complete remission (CR) rate in one course of induction chemotherapy was analyzed by combineation with clinical characteristics.
RESULTS:
34 kinds of genes in bone marrow or peripheral blood of 43 patients were detected by high throughput sequencing and the gene mutations were detected in 16 out of 34 genes. The mutation rate of KIT gene was the highest (48.8%), followed by NRAS (16.3%), ASXL1 (16.3%), TET2 (11.6%), CSF3R (9.3%), FLT3 (9.3%), KRAS (7.0%). The detection rates of mutations in different functional genes were as follows: genes related with signal transduction pathway (KIT, FLT3, CSF3R, KRAS, NRAS, JAK2, CALR, SH2B3, CBL) had the highest mutation frequency (72.1% (31/43); epigenetic modification gene mutation frequency was 30.2% (13/43), including ASXL1, TET2, BCOR); transcriptional regulation gene mutation frequency was 7.0% (3/43), including ETV6, RUNX1, GATA2). Splicing factor related gene mutation frequency was 2.3% (1/43), including ZRSR2). The CR rate was 74.4% after one course of induction chemotherapy. At first diagnosis, patients with low expression of WT1 (the median value of WT1 was 788.9) were more likely to get CR (P=0.032) and the RFS of patients who got CR after one course of induction chemotherapy was significantly longer than that of patients without CR [7.6 (2.2-44.1) versus 5.8 (1-19.4), (P=0.048)]. The rate of CR in the signal transduction pathway gene mutation group was significantly lower than that in non-mutation group (64.5% vs 100%) (P=0.045), while the level of serum hydroxybutyrate dehydrogenase (HBDH) was significantly higher than that in non-mutation group [(418 (154-2702) vs 246 (110-1068)] (P=0.032). There was no difference in CD56 expression between the two groups (P=0.053), which was limited to the difference between (≥20%) expression and non-expression. (P=0.048).
CONCLUSION
CBF-AML patients with signal transduction pathway gene mutation are often accompanied by high HBDH level and CD56 expression, moreover, the remission rate induced by one course of treatment is low.
High-Throughput Nucleotide Sequencing
;
Humans
;
Leukemia, Myeloid, Acute
;
Mutation
;
Prognosis
;
Signal Transduction
9.To compare the efficacy and incidence of severe hematological adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia.
Xiao Shuai ZHANG ; Bing Cheng LIU ; Xin DU ; Yan Li ZHANG ; Na XU ; Xiao Li LIU ; Wei Ming LI ; Hai LIN ; Rong LIANG ; Chun Yan CHEN ; Jian HUANG ; Yun Fan YANG ; Huan Ling ZHU ; Ling PAN ; Xiao Dong WANG ; Gui Hui LI ; Zhuo Gang LIU ; Yan Qing ZHANG ; Zhen Fang LIU ; Jian Da HU ; Chun Shui LIU ; Fei LI ; Wei YANG ; Li MENG ; Yan Qiu HAN ; Li E LIN ; Zhen Yu ZHAO ; Chuan Qing TU ; Cai Feng ZHENG ; Yan Liang BAI ; Ze Ping ZHOU ; Su Ning CHEN ; Hui Ying QIU ; Li Jie YANG ; Xiu Li SUN ; Hui SUN ; Li ZHOU ; Ze Lin LIU ; Dan Yu WANG ; Jian Xin GUO ; Li Ping PANG ; Qing Shu ZENG ; Xiao Hui SUO ; Wei Hua ZHANG ; Yuan Jun ZHENG ; Qian JIANG
Chinese Journal of Hematology 2023;44(9):728-736
Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult
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Humans
;
Adolescent
;
Imatinib Mesylate/adverse effects*
;
Incidence
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Antineoplastic Agents/adverse effects*
;
Retrospective Studies
;
Pyrimidines/adverse effects*
;
Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy*
;
Treatment Outcome
;
Benzamides/adverse effects*
;
Leukemia, Myeloid, Chronic-Phase/drug therapy*
;
Aminopyridines/therapeutic use*
;
Protein Kinase Inhibitors/therapeutic use*