1. Characteristics of FLT3 gene mutation and clinical efficacy of tyrosine kinase inhibitor in patients with mixed phenotype acute leukemia
Yu ZHANG ; Yang ZHANG ; Fang WANG ; Mingyu WANG ; Hong LIU ; Panxiang CAO ; Xiaoli MA ; Xue CHEN ; Wen TENG ; Xian ZHANG ; Mangju WANG ; Hongxing LIU
Journal of Leukemia & Lymphoma 2020;29(1):37-40
Objective:
To analyze the incidence and mutation characteristics of FLT3 gene mutation and clinical efficacy of tyrosine kinase inhibitor (TKI) in patients with mixed phenotype acute leukemia (MPAL).
Methods:
A total of 48 patients with MPAL who were admitted to Hebei Yanda Lu Daopei Hospital from June 2015 to February 2018 were retrospectively analyzed. The common mutated 58 genes in hematologic malignancies were detected by using amplicon-targeted next generation sequencing, of which internal tandem duplication (ITD) and point mutation occurred in the hotspot region of exon 14, 15 and 20 in FLT3 gene. Multiplex polymerase chain reaction (PCR) analysis was used to detect 35 gene fusions in hematological neoplams.
Results:
There were 7 cases of FLT3 mutation in 48 MPAL patients, which were all ITD mutations. The median length of the inserts of FLT3-ITD was 48 bp, and one MPAL patient carried 2 multiple length inserts simultaneously, and the median variant allele frequency (VAF) was 40.5% (7.9%-84.7%). There were no statistically significant differences in clinical and genetic characteristics between FLT3 mutation-positive and FLT3 mutation-negative MPAL patients (both
2.Fanconi anemia gene-associated germline predisposition in aplastic anemia and hematologic malignancies.
Daijing NIE ; Jing ZHANG ; Fang WANG ; Xvxin LI ; Lili LIU ; Wei ZHANG ; Panxiang CAO ; Xue CHEN ; Yang ZHANG ; Jiaqi CHEN ; Xiaoli MA ; Xiaosu ZHOU ; Qisheng WU ; Ming LIU ; Mingyue LIU ; Wenjun TIAN ; Hongxing LIU
Frontiers of Medicine 2022;16(3):459-466
Whether Fanconi anemia (FA) heterozygotes are predisposed to bone marrow failure and hematologic neoplasm is a crucial but unsettled issue in cancer prevention and family consulting. We retrospectively analyzed rare possibly significant variations (PSVs) in the five most obligated FA genes, BRCA2, FANCA, FANCC, FANCD2, and FANCG, in 788 patients with aplastic anemia (AA) and hematologic malignancy. Sixty-eight variants were identified in 66 patients (8.38%). FANCA was the most frequently mutated gene (n = 29), followed by BRCA2 (n = 20). Compared with that of the ExAC East Asian dataset, the overall frequency of rare PSVs was higher in our cohort (P = 0.016). BRCA2 PSVs showed higher frequency in acute lymphocytic leukemia (P = 0.038), and FANCA PSVs were significantly enriched in AA and AML subgroups (P = 0.020; P = 0.008). FA-PSV-positive MDS/AML patients had a higher tumor mutation burden, higher rate of cytogenetic abnormalities, less epigenetic regulation, and fewer spliceosome gene mutations than those of FA-PSV-negative MDS/AML patients (P = 0.024, P = 0.029, P = 0.024, and P = 0.013). The overall PSV enrichment in our cohort suggests that heterozygous mutations of FA genes contribute to hematopoietic failure and leukemogenesis.
Anemia, Aplastic/genetics*
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Epigenesis, Genetic
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Fanconi Anemia/genetics*
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Germ Cells
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Hematologic Neoplasms/genetics*
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Humans
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Leukemia, Myeloid, Acute/genetics*
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Retrospective Studies
3.Mutation profiling of 16 candidate genes in de novo acute myeloid leukemia patients.
Yang ZHANG ; Fang WANG ; Xue CHEN ; Wenjing LIU ; Jiancheng FANG ; Mingyu WANG ; Wen TENG ; Panxiang CAO ; Hongxing LIU
Frontiers of Medicine 2019;13(2):229-237
This retrospective analysis aimed to investigate the mutation profile of 16 common mutated genes in de novo acute myeloid leukemia (AML) patients. A total of 259 patients who were diagnosed of de novo AML were enrolled in this study. Mutation profiling of 16 candidate genes were performed in bone marrow samples by using Sanger sequencing.We identified at least 1 mutation in 199 of the 259 samples (76.8%), and 2 or more mutations in 31.7% of samples. FLT3-ITD was the most common mutated gene (16.2%, 42/259), followed by CEBPA (15.1%, 39/259), NRAS (14.7%, 38/259), and NPM1 (13.5%, 35/259). Concurrence was observed in 97.1% of the NPM1 mutated cases and in 29.6% of the double mutated CEBPA cases. Distinct patterns of co-occurrence were observed for different hotspot mutations within the IDH2 gene: R140 mutations were associated with NPM1 and/or FLT3-ITD mutations, whereas R172 mutations co-occurred with DNMT3A mutations only. Concurrence was also observed in 86.6% of epigenetic regulation genes, most of which co-occurred with NPM1 mutations. The results showed certain rules in the mutation profiling and concurrence of AML patients, which was related to the function classification of genes. Defining the mutation spectrum and mutation pattern of AML will contribute to the comprehensive assessment of patients and identification of new therapeutic targets.
Adolescent
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Adult
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Aged
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CCAAT-Enhancer-Binding Proteins
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genetics
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Child
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Child, Preschool
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China
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DNA Mutational Analysis
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Female
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GTP Phosphohydrolases
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genetics
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Gene Expression Profiling
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Gene Frequency
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Genetic Predisposition to Disease
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Humans
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Kaplan-Meier Estimate
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Leukemia, Myeloid, Acute
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genetics
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Male
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Membrane Proteins
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genetics
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Middle Aged
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Mutation
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Nuclear Proteins
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genetics
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Phenotype
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Retrospective Studies
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Young Adult
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fms-Like Tyrosine Kinase 3
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genetics
4. Application progress of transcriptome sequencing in hematological malignancies
Hongxing LIU ; Xue CHEN ; Fang WANG ; Xiaoli MA ; Lili YUAN ; Panxiang CAO ; Daijing NIE
Journal of Leukemia & Lymphoma 2019;28(12):705-708
Transcriptome sequencing (RNA-seq) has unique advantages in analyzing gene fusion, splicing mutations, and gene expression profiles. Single-cell RNA-seq provides powerful tools to reveal cellular heterogeneity in normal and tumor tissues. With the widespread application of high-throughput gene sequencing technology and the rapid reduction in cost, RNA-seq is increasingly used in hematological malignancies research. This article introduces the related research progress in conjunction with reports at the 61st American Society of Hematology Annual Meeting.
5. Progress of big data analysis and artificial intelligence technology for hematologic neoplasms
Hongxing LIU ; Xiaosu ZHOU ; Fang WANG ; Panxiang CAO ; Jiancheng FANG
Journal of Leukemia & Lymphoma 2020;29(1):17-19
The new wave of artificial intelligence pushed by deep learning algorithms has dramatically promoted the development of big data analysis technology. On the other hand, advances in life sciences represented by high-throughput genome sequencing have provided massive medical data. Artificial intelligence technology has also provided a powerful tool for hematological malignancy research. This article introduces related research progress in the 61st American Society of Hematology Annual Meeting.
6.A Single-Center Analysis of the Use of G-CSF Combined with Plerixafor to Mobilize Peripheral Blood Hematopoietic Stem Cell from Healthy Related Donors in Allogeneic Hematopoietic Stem Cell Transplantation.
Juan CHEN ; Li-Li YUAN ; Xian ZHANG ; Jia-Li QIAO ; Qing-Xue YIN ; Yue-Mei ZHANG ; Xue-Lian YANG ; Xing-Yu CAO
Journal of Experimental Hematology 2022;30(1):286-291
OBJECTIVE:
To study the effect and safety of G-CSF combined with Plerixafor on the mobilization of peripheral blood hematopoietic stem cells from healthy related donors of allogeneic hematopoietic stem cell transplantation (allo-HSCT).
METHODS:
It was analyzed retrospectively that the data of peripheral blood hematopoietic stem cells from 33 (observation group) related donors mobilized by G-CSF plus Plerixafor in Hebei Yanda Lu Daopei Hospital from April 2019 to April 2021. Bone marrow and peripheral blood hematopoietic stem cells (PBSCs) of these donors were respectively collected on the fourth and fifth day of G-CSF-induced mobilization. Following the administration of Plerixafor on the night of the fifth day, PBSCs were collected on the sixth day once again. 46 donors using "G-CSF only" mobilization method in the same period were randomly selected as the control and respectively analyzed the differences of CD34+ cell counts on the fifth and the sixth day in two groups. And the donors' adverse reaction to Plerixafor in the form of questionnaire was also observed. Then it was compared that the patients who underwent allo-HSCT in "G-CSF+Plerixafor" group and "G-CSF only" group in terms of acute GVHD at grade I-IV or III-IV, CMV reactivation and EBV reactivation.
RESULTS:
CD34+ cells count (M±Q) among PBSCs collected on the fifth and the sixth day in the observation group were (1.71±1.02)×106/kg and (4.23±2.33)×106/kg, respectively. CD34+ cell counts on the sixth day was significantly higher than that of the fifth day (P<0.001); While the counterparts in the control group were (2.47±1.60)×106/kg and (1.87±1.37)×106/kg, respectively. By statistical analysis, CD34+ cell counts on the sixth day was significantly less than that of the fifth day (P<0.001). The adverse reaction to Plerixafor for the donors in the study were all grade 1 or 2 (mild or moderate) according to CTCAE 5.0 and disappeared in a short time. The patients who underwent allo-HSCT in the "G-CSF+Plerixafor" group and "G-CSF only" group were not statistically significant in terms of acute GVHD at grade I-IV or III-IV, CMV reactivation and EBV reactivation (P>0.1).
CONCLUSION
The cell mobilization program of G-CSF combined with Plerixafor is safe and effective for being applied to allo-HSCT. The addition of Plerixafor can significantly increase the number of CD34 postive cells in the PBSC collection. Key words ; ;
Antigens, CD34
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Benzylamines
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Cyclams
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Granulocyte Colony-Stimulating Factor
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Hematopoietic Stem Cell Mobilization
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Hematopoietic Stem Cell Transplantation
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Hematopoietic Stem Cells
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Heterocyclic Compounds
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Humans
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Peripheral Blood Stem Cell Transplantation
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Retrospective Studies
7. Application of metagenomics next-generation sequencing in monitoring Legionella pneumophila infection after allogeneic hematopoietic stem cell transplantation
Lili YUAN ; Huizheng ZHAO ; Jianping ZHANG ; Fang WANG ; Nannan LI ; Xingzhen ZHAO ; Xue CHEN ; Yang ZHANG ; Daijing NIE ; Panxiang CAO ; Mangju WANG ; Ming LIU ; Mingyue LIU ; Hongxing LIU
Journal of Leukemia & Lymphoma 2019;28(12):734-738
Objective:
To investigate the application of metagenomic next-generation sequencing (mNGS) in detection of the rare or difficult-to-cultivate pathogens.
Methods:
One patient with acute lymphoblastic leukemia who went through allogeneic hematopoietic stem cell transplantation (allo-HSCT) developed symptoms of infection after transplantation. Conventional microbial culture, polymerase chain reaction (PCR), and mNGS combined with biological information analysis were performed with plasma and cerebrospinal fluid samples, the anti-infective treatment was adjusted according to the test results, and the efficacy was assessed.
Results:
No suspected pathogens were detected by microbial culture and PCR in the cerebrospinal fluid and plasma samples since the patient developed infection symptoms. However, Legionella pneumophila was analyzed by mNGS in the cerebrospinal fluid specimen on day 23 after allo-HSCT (reads count: 19 655), and it was considered as the principal pathogen after comprehensively evaluating the patient's clinical manifestations and the test results. Then the antimicrobial treatments were adjusted according to the patient's clinical manifestations and laboratory test results, and the number of gene sequences of Legionella pneumophila was monitored by mNGS method. Azithromycin, tigecycline, and other antibiotics effective for Legionella pneumophila were used after detecting this pathogen. A total of 15 mNGS analysis were performed during the 5-month period, and the highest number of Legionella pneumophila sequences monitored in the cerebrospinal fluid was 2 226, the lowest was 253 and eventually turned negative. The clinical symptoms and treatment outcomes were consistent with the mNGS monitoring results.
Conclusions
The mNGS technology has significant value in detection of the rare and difficult-to-cultivate pathogens. The mNGS technology provides a valuable supplement to microbial culture and PCR methods.
8.Analysis of Human Herpes Viruses-Activated Infection Spectra in Patients with Various Immunodeficiencies.
Li-Li YUAN ; Fang WANG ; Xue CHEN ; Yang ZHANG ; Jian-Ping ZHANG ; Jun-Fang YANG ; Juan DING ; Cheng-Liang ZHEN ; Meng-Nan WANG ; Dan-Na CHEN ; Lu-You HAN ; Pei-Yu LI ; Yuan-Li HE ; Hong-Xing LIU
Journal of Experimental Hematology 2020;28(1):314-319
OBJECTIVE:
To study the epidemiologic characteristics of human herpes virus (HHV) activated infection in the diseases of blood system and patients received allo-HSCT by statistically analyzing the screening results of 8 human herpes viruses (HHVs) of 4164 patients in Hebei Yanda LU Dao-Pei Hospital from 2012 to 2017.
METHODS:
PCR was used to screen 8 HHVs.
RESULTS:
Two thousand and fifty-two patients (49.28%) were HHV-positive among 4164 patients screened. Among these patients screened, the infection spectra of 8 human HHVs in hematological diseases as well as patients received allogeneic hematopoietic stem cell transplantation of totally 2994 patients were summarized as follows: the positive rate of EBV (29.49%) was the highest, that of HCMV (23.15%), HHV-6 was 18.77% and HHV-7 was 17.64%, while the remaining 4 HHVs all≤2.1%. The rate of co-infection of various HHVs was significantly higher than that of single infection of HHV among all these disease groups except familial hemophagocytic lymphohistiocytosis, for which single EBV infection was the most common. The differences of positive rates among these 8 human HHVs in hematological diseases as well as patients received allogeneic hematopoietic stem cell transplantation were statistically significant by Chi-square test of R*C tables (χ=54.99, P<0.05). For each HHV, the differences of positive rates among the above-mentioned disease groups were also statistically significant except HHV-8 (P<0.05).
CONCLUSION
The patients with various blood diseases have different activated infection spectra of HHVs. EBV, HCMV, HHV-6 and HHV-7 are most common in HHVs infection. Different HHVs infections correlate with different hematologion diseases.
9. Efficacy and safety observation of apatinib in treatment of advanced gastric cancer
Zhihui HE ; Jiangzheng ZENG ; Fen HUANG ; Junhua LEI ; Yanda LU
Cancer Research and Clinic 2019;31(12):814-817
Objective:
To investigate the effect and safety of apatinib in the treatment of advanced gastric cancer.
Methods:
A total of 60 patients with advanced gastric cancer at the first Affiliated Hospital of Hainan Medical College from April 2015 to October 2018 were retrospectively analyzed, and all patients were divided into two groups according to the treatment method, each group of 30 cases. The control group was treated with conventional treatment, and the observation group was given the treatment of apatinib on the basis of the control group, and then the clinical curative effect and adverse reactions were compared between the two groups.
Results:
There were 2 cases (6.67%) of complete remission in the observation group, 14 cases (46.67%) of partial remission, 10 cases (33.33%) of stability and 4 cases (13.33%) of disease progression, and the total effective rate was 53.33% (16/30). The control group had no complete remission, 8 cases (26.67%) of partial remission, 11 cases (36.67%) of stability and 11 cases (36.67%) of disease progression, and the total effective rate was 26.67% (8/30). The difference of total effective rate between the two groups was statistically significant (χ 2 = 4.444,
10.Efficacy comparison of erlotinib and pemetrexed in treatment of advanced non-small cell lung cancer
Zhihui HE ; Jiangzheng ZENG ; Fen HUANG ; Junhua LEI ; Yanda LU
Cancer Research and Clinic 2019;31(8):540-544
Objective To compare the efficacy of erlotinib and pemetrexed in treatment of advanced non-small cell lung cancer (NSCLC) and its effect on the immunity of patients. Methods A total of 82 patients with NSCLC at the First Affiliated Hospital of Hainan Medical College from June 2014 to May 2018 were retrospectively analyzed. According to the different treatment methods, the patients were divided into erlotinib group (150 mg/d, oral administration, 2 hours after the meal) and pemetrexed group (500 mg/m2, intravenous drip, 21-day each cycle). There were 41 cases in each group. The clinical effects of the two groups were analyzed. Flow cytometry was used to detect the immune index. Results The objective effective rate in pemetrexed group was lower than that in erlotinib group [34.2% (14/41) vs. 39.0% (16/41), χ 2 = 0.210, P =0.647). There was no significant difference in T lymphocyte subsets between the two groups before and after treatment (both P > 0.05). The values of CD3+ T cells, CD4+ T cells, CD4+ / CD8+ in both groups after the treatment were decreased compared with the values before the treatment; CD8 + T cells was increased after the treatment compared with the value before the treatment (all P < 0.05). Quality of life questionnaire-C30 (QLQ-C30) score in erlotinib group was higher than that in pemetrexed group [(75.1±13.5) vs. (68.9±12.9), t = 2.158, P = 0.017]. Myelosuppression and gastrointestinal reactions were the main adverse events in pemetrexed group; rashes and diarrhoea were the main adverse reactions in erlotinib group. Grade Ⅰ-Ⅱ side effects occurred in both groups. There were statistical differences in the incidence of myelosuppression, gastrointestinal reactions, rashes and diarrhoea of both groups (all P < 0.05). Conclusions The efficacy oferlotinib and pemetrexed in treatment of advanced NSCLC is similar, and both of them could regulate the immune response. Erlotinib has a significant advantage in improving the quality of life.