Publications by authors named "Yanhong Tan"

30 Publications

  • Page 1 of 1

The clinical characteristics and prognosis of Chinese acute myeloid leukemia patients with CSF3R mutations.

Int J Lab Hematol 2021 Nov 24. Epub 2021 Nov 24.

Shanxi Medical University, Taiyuan, China.

Introduction: The colony-stimulating factor 3 receptor (CSF3R) controls the proliferation of myeloid progenitors and differentiation into neutrophils. However, the clinical features and prognostic significance of CSF3R mutations in primary acute myeloid leukemia (AML) patients are still unclear.

Methods: 158 newly diagnosed AML patients were retrospectively evaluated in our study. Amplicon-based next-generation sequencing (NGS) and multiplex-nested reverse-transcription polymerase chain reaction (RT-PCR) were used to investigate the 34 genes and 43 fusion genes associated with leukemia. In addition, clinical features, mutation incidence, and survival outcomes were compared between patients with CSF3R mutation and patients with wild-type CSF3R.

Results: In our study, CSF3R mutations were found in 7.6% (12/158) cases. The membrane-proximal amino acid substitution T618I (58.3%) was the most frequent mutation. CSF3R mutations were associated with higher WBC counts (P = .035). CEBPA mutation, TET2 mutation, and RUNX1-RUNX1T1 translocation were the most common co-mutations of CSF3R. The CSF3R gene was mutually exclusive with signal transduction genes (P = .029), while positively associated with TET2 mutations (P = .014). CSF3R mutations had no effect on CR1 (P = .935), R (P = .625) and OS (P = .1172). Patients with CSF3R mutations had a worse DFS (P = .0352) than those with wild-type CSF3R. Multivariate survival analysis showed that CSF3R mutation was an independent risk factor for DFS of primary AML patients (HR=2.048, 95%CI: 1.006-4.170, P = .048).

Conclusion: AML patients with CSF3R mutations had unique clinical features and gene co-mutation spectrum. CSF3R mutation was an independent risk factor for DFS and could be a potential prognostic marker and therapeutic target for Chinese primary AML patients.
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http://dx.doi.org/10.1111/ijlh.13762DOI Listing
November 2021

GATA2 rs2335052 and GATA2 rs78245253 single-nucleotide polymorphisms in Chinese patients with acute myelocytic leukemia.

Int J Lab Hematol 2021 Dec 9;43(6):1491-1500. Epub 2021 Aug 9.

Institute of Hematology, the Second Hospital of Shanxi Medical University, Taiyuan, China.

Introduction: GATA binding protein 2 (GATA2) gene, involved in progression of hematologic malignancies and various solid tumors, is a susceptibility gene for inherited acute myeloid leukemia (AML). However, the influence of its single-nucleotide polymorphisms (SNPs) on AML remains unknown.

Methods: We used allele-specific PCR to genotype GATA2 rs2335052 and rs78245253 in 159 newly diagnosed AML (non-M3) patients and 300 healthy volunteers, and all of participants came from China. And 34 common hematological tumor gene mutations in 159 AML patients were detected by next-generation sequencing. Kaplan-Meier survival analysis and Cox proportional hazard regression were used to analyze the association between the two SNPs and the prognosis of AML.

Results: We found GATA2 rs2335052 C/T genotype, rs2335052 T/T genotype and rs78245253 G/C genotype in 51.6%, 13.8% and 11.3% AML patients. Our results demonstrated that GATA2 rs2335052 and rs78245253 were associated with certain laboratory features in AML patients, which had no effect on the pathogeny, chemotherapy response and recurrence of patients. Nevertheless, Kaplan-Meier survival analysis showed that, compared with rs78245253 G/G genotype, rs78245253 G/C genotype was significantly related to a decrease in overall survival (OS) (P = .020). Additionally, multivariate cox regression analysis showed that GATA2 rs78245253 was an independent risk factor for OS of AML patients in China.

Conclusion: GATA2 rs78245253 was an independent predictor for prognosis of AML patients in China and may be used as a potential indicator to predict the survival of AML patients in China. Further studies are needed to validate these findings and clarify the underlying mechanism.
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http://dx.doi.org/10.1111/ijlh.13649DOI Listing
December 2021

The clinical characteristics and prognosis of cytogenetically normal AML with single mutations of CEBPA.

Int J Lab Hematol 2021 Dec 3;43(6):1424-1431. Epub 2021 Jul 3.

Institute of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan, China.

Introduction: CEBPA mutation is a common mutation in normal karyotype AML. CEBPAdm AML has been recognized as a separate entity, but there is still controversy to the prognosis of CEBPAsm patients.

Methods: A total of 151 newly diagnosed cytogenetically normal AML patients treated at the Second Hospital Center of Shanxi Medical University from February 2017 to December 2019 were the subjects of the study. According to the number of mutations in the CEBPA gene, the patients were divided into three groups, CEBPAsm, CEBPAdm, and CEBPAwt patients. The clinical characteristics, gene mutations, response, and prognosis were retrospectively compared among the three groups.

Results: CEBPAsm patients had lower hemoglobin values compared to CEBPAdm (P = .049). There was no statistical difference between the CEBPAsm cases and the CEBPAdm cases in the mutation types and the distribution of mutation regions (P > .050). Compared with CEBPAdm, cases with CEBPAsm were more likely associated with multiple other gene mutations (P = .023). Patients with CEBPAdm had a higher CR, ORR, and OS than those CEBPAwt (P < .050). CEBPAsm patients had a similar OS with CEBPAdm and CEBPAwt patients (P = .281). These CEBPAsm patients with VAF<30% had lower OS than the patients with VAF≥30%. FLT3-ITD mutations could reduce CEBPAsm patients' OS (P = .019).

Conclusion: Our data first highlighted the impact of CEBPAsm VAF on OS, and the results showed the lower the VAF was, the shorter the OS tended to. The VAF of CEBPAsm could provide specific significance in some extent for the prognosis of patients.
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http://dx.doi.org/10.1111/ijlh.13612DOI Listing
December 2021

A lineage switch from NPM1-mutant acute myeloid leukemia to acute T-cell lymphoblastic leukemia with KMT2D and ARID2 mutant.

Int J Lab Hematol 2021 08 21;43(4):O230-O233. Epub 2021 Apr 21.

The Haematology Department, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.

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http://dx.doi.org/10.1111/ijlh.13534DOI Listing
August 2021

Functional analysis of atypical mutations in exons 13 and 15 of JAK2 gene in myeloproliferative neoplasms.

Int J Lab Hematol 2021 06 27;43(3):e110-e113. Epub 2020 Nov 27.

Institute of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan, China.

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http://dx.doi.org/10.1111/ijlh.13398DOI Listing
June 2021

Monitoring Treatment-Free Remission by Droplet Digital PCR in CML Patients with Deep Molecular Response to Tyrosine Kinase Inhibitor: An Analysis Based on Real-World Data.

Ann Clin Lab Sci 2020 Sep;50(5):591-599

Department of Hematology, the Second Hospital of Shanxi Medical University, Taiyuan, China

Treatment-free remission (TFR) is emerging as a new therapy goal for chronic myeloid leukemia (CML) patients in the tyrosine kinase inhibitors (TKI) era. Data indicates the unfavorable success rate of TFR. This study aimed to compare and evaluate the clinical value of dd-PCR in predicting relapse in CML patients entering TFR. Using dd-PCR and RT-qPCR technology, dynamic BCR/ABL transcripts were detected in 13 CML patients who discontinued TKI treatment after sustaining undetectable BCR-ABL levels for a median time of 25 months. The results showed that in 13 patients, only 2 cases (22.2%) of 9 patients who executed planned discontinuation achieved TFR within 12 months. In the first 6 months, the detection rate of BCR/ABL transcripts by dd-PCR was higher than that by RT-qPCR and the two methods kept a positive correlation (r=0.9651, =0.0349). Meanwhile, the time of detectable BCR/ABL by dd-PCR were significantly shorter (<0.05), which was an average of 2.98 months earlier than RT-qPCR. The total TKI therapy and MR4.5 duration time related with TFR were longer in patients with intermediate or high Sokal risk scores (<0.05). The dd-PCR could be more sensitive than RT-qPCR for monitoring BCR/ABL transcripts of CML patients with deep molecular response to TKI. The technique can be used as a preferred method to detect the transcripts in the first 6 months after TKI cessation.
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September 2020

Identification of Two Novel Truncated Transcripts of Janus Kinase 2 Gene.

Ann Clin Lab Sci 2020 Jul;50(4):497-503

Institute of Hematology, the Second Hospital of Shanxi Medical University

Jak2 is a nonreceptor tyrosine kinase that plays a critical role in signal transduction through an abundance of receptors, such as erythropoietin receptor. In this paper, we report two previously unknown transcripts of Jak2 gene. One transcript deletes the 77nt of 3' end exon 10 of the Jak2 gene, resulting in a frameshift that introduces a stop codon in the downstream exon and produces a truncated protein of 421 amino acids if translated. The other transcript skips the entire exon 10, leading to a premature stop codon in the adjacent exon 11, producing a truncated protein of 414 amino acids if translated. Therefore, the physiological significance of the expression of two novel transcripts in healthy volunteers and patients with myeloproliferative neoplasms, acute leukemia, and chronic myeloid leukemia needs to be investigated further.
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July 2020

Disulfiram/cytarabine eradicates a subset of acute myeloid leukemia stem cells with high aldehyde dehydrogenase expression.

Leuk Res 2020 Mar 19;92:106351. Epub 2020 Mar 19.

Institute of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan, China. Electronic address:

Most patients with acute myeloid leukemia (AML) achieve complete remission (CR) after induction chemotherapy, however, in some patients, the disease subsequently relapses and may lead to death. Leukemia stem cells (LSC) have been identified as the main cause for recurrence. Increased aldehyde dehydrogenase (ALDH) activity in a variety of cancer stem cells prevents effective action of chemotherapeutic drugs. In this study, we found that approximately 50.7% of AML patients had ALDH, and the presence of ALDH stem cells was associated with poor cytogenetic prognosis. Lentiviral vector transduced ALDH leukemia cell lines are insensitive to the conventional chemotherapy drug cytarabine, and inhibition of ALDH activity by disulfiram (DSF) can increase the sensitivity of ALDH leukemia cells to cytarabine. Unlike traditional chemotherapy drugs, DSF is not toxic to healthy umbilical cord blood stem cells. An ALDH leukemia cell xenograft model was established using immunodeficient mice to mimic the disease environment, and DSF and cytarabine were found to eliminate the ALDH leukemia cells in transplanted mice while not affecting the healthy blood cells of mice. These findings suggest that DSF may have therapeutic potential by inhibiting ALDH activity and thereby increasing chemosensitivity.
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http://dx.doi.org/10.1016/j.leukres.2020.106351DOI Listing
March 2020

Coagulopathy in cytogenetically and molecularly distinct acute leukemias at diagnosis: Comprehensive study.

Blood Cells Mol Dis 2020 03 30;81:102393. Epub 2019 Nov 30.

Department of Hematology, the Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China. Electronic address:

We analyzed the characteristics of coagulopathy in cytogenetically and molecularly distinct acute leukemias. We retrospectively analyzed 211 adult patients with de novo non-acute promyelocytic leukemia (APL) and acute myeloid leukemia (AML), and 105 newly diagnosed patients with B-cell acute lymphoblastic leukemia (B-ALL). Disseminated intravascular coagulation (DIC) occurrence was assessed according the International Society of Thrombosis and Haemostasis (ISTH) criteria. Further, we analyzed the associations of the cytogenetics and mutations with DIC development and coagulation profile. Significant differences were observed between APL and non-APL AML (P = 0.001), APL and B-ALL (P = 0.002), and non-APL AML and B-ALL (P = 0.009) in the distribution of ISTH DIC scores of the acute leukemia patients that met the criteria for diagnosis of DIC. Except for the elevated leukocyte count, a normal karyotype with NPM1 mutations or/and FLT3-ITD mutations was independently associated with the development of DIC in non-APL AML, characterized by significant PT prolongation and significantly elevated D-Dimers. The P210 transcript strongly predicted hypofibrinogenemia in B-ALL in the final multivariate model, but Philadelphia chromosome negatively affected elevated D-dimers. In conclusion, DIC occurrence and the coagulation profile were associated with the cytogenetics and mutations in acute leukemia.
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http://dx.doi.org/10.1016/j.bcmd.2019.102393DOI Listing
March 2020

Inhibition of the Nrf2-TrxR Axis Sensitizes the Drug-Resistant Chronic Myelogenous Leukemia Cell Line K562/G01 to Imatinib Treatments.

Biomed Res Int 2019 18;2019:6502793. Epub 2019 Nov 18.

Department of Hematology, 2nd Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China.

Nuclear factor erythroid 2-related factor 2 (Nrf2) is involved in tumor drug resistance, but its role in imatinib resistance of chronic myeloid leukemia (CML) remains elusive. We aimed to investigate the effects of Nrf2 on drug sensitivity, thioredoxin reductase (TrxR) expression, reactive oxygen species (ROS) production, and apoptosis induction in imatinib-resistant CML K562/G01 cells and explored their potential mechanisms. Stable K562/G01 cells with knockdown of Nrf2 were established by infection of siRNA-expressing lentivirus. The mRNA and protein expression levels of Nrf2 and TrxR were determined by real-time quantitative polymerase chain reaction and western blot, respectively. ROS generation and apoptosis were assayed by flow cytometry, while drug sensitivity was measured by the Cell Counting Kit-8 assay. Imatinib-resistant K562/G01 cells had higher levels of Nrf2 expression than the parental K562 cells at both mRNA and protein levels. Expression levels of Nrf2 and TrxR were positively correlated in K562/G01 cells. Knockdown of Nrf2 in K562/G01 cells enhanced the intracellular ROS level, suppressed cell proliferation, and increased apoptosis in response to imatinib treatments. Nrf2 expression contributes to the imatinib resistance of K562/G01 cells and is positively correlated with TrxR expression. Targeted inhibition of the Nrf2-TrxR axis represents a potential therapeutic approach for imatinib-resistant CML.
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http://dx.doi.org/10.1155/2019/6502793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885806PMC
April 2020

A new griseofulvin derivative from a soft coral-derived fungus sp. SCSIO41208.

Nat Prod Res 2020 Oct 8;34(20):2971-2975. Epub 2019 Apr 8.

Key Laboratory of Marine Bio-resources Sustainable Utilization/Guangdong Key Laboratory of Marine Materia Medica/Research Center for Marine Microbes, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, P. R. China.

A new griseofulvin derivative, eupenigriseofulvin (), together with six known compounds, griseofulvin (), dechlorogriseofluvin (), dechloroisogriseofulvin (), trichopyrone (), 2-(4-hydroxyphenyl)-ethanol (), and 1-phenylethane-1,2-diol (), were isolated from the EtOAc extract of sp. SCSIO41208. The structures of these compounds were elucidated by spectroscopic methods including NMR and mass spectrometry. The absolute configuration of was determined on the basis of electronic circular dichroism (ECD) data analysis.
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http://dx.doi.org/10.1080/14786419.2019.1596093DOI Listing
October 2020

TET2 rs2454206, TET2 rs12498609 and ASXL1 rs3746609 single nucleotide polymorphisms in patients with myelodysplastic syndromes.

Blood Cells Mol Dis 2019 02 7;74:44-50. Epub 2018 Nov 7.

Department of Hematology, The Second Hospital of Shanxi Medical University,382 Wuyi St, Taiyuan, Shanxi, China. Electronic address:

To study the association between TET2rs2454206, TET2rs12498609 and ASXL1rs3746609 and Myelodysplastic syndromes (MDS), a total of 90 MDS patients and 143 healthy volunteers were included. The clinical data, bone marrow samples of patients and peripheral blood samples of volunteers were obtained. We found TET2rs2454206 G/A genotype, TET2rs12498609 G/C genotype and ASXL1rs3746609 A/G genotype in 13.3%, 11.1%, 10.1% MDS patients and in 42.7%, 22.4%, 23.8% healthy volunteers (P < 0.001; P = 0.029; P = 0.009, respectively). TET2 rs2454206 G/A genotype was associated with higher serum LDH level in MDS (P = 0.025). Patients with TET2rs12498609 G/C genotype were characterized with higher frequency of mutated SRSF2 gene (P = 0.042) and lower occurrence rate of anemia (P = 0.026) than those with C/C genotype. ASXL1rs3746609 A/G genotype linked with higher thrombocyte counts (P = 0.02) and percent of total T lymphocyte (P = 0.029), whereas with lower percent of NK cell (P = 0.032) and B lymphocyte (P = 0.007). None of these three SNPs had impact on the overall survival and disease progression to AML. We concluded that People with TET rs2454206 G/A genotype, TET2rs12498609 G/C genotype or ASXL1rs3746609 A/G genotype were related to lower prevalence of MDS. All of the three SNPs were associated with certain laboratory features in MDS patients.
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http://dx.doi.org/10.1016/j.bcmd.2018.11.002DOI Listing
February 2019

The CD9 CD11b HLA-DR immunophenotype can be used to diagnose acute promyelocytic leukemia.

Int J Lab Hematol 2019 Apr 13;41(2):168-175. Epub 2018 Oct 13.

The Haematology Department, The Second Hospital of Shanxi Medical University, Taiyuan City, Shanxi Province, China.

Objective: To investigate the immunophenotypic characteristics of acute promyelocytic leukemia (APL) and explore the sensitivity and specificity of various antibody combinations for the timely and accurate diagnosis APL.

Methods: A retrospective analysis was performed using morphological, immunological, genetic, and molecular biological data from 92 patients diagnosed with APL and 190 controls diagnosed with non-APL acute myeloid leukemia.

Results: For APL diagnosis, the CD9/CD11b/human leukocyte antigen (HLA)-DR antibody combination had 85% sensitivity and 95% specificity, AUC = 0.85. However, the sensitivity and specificity were 39% and 92%, AUC = 0.65, respectively, for the HLA-DR/CD34/CD117 combination, and 80% and 80%, AUC = 0.80, respectively for the CD11b/HLA-DR combination. Significant differences were observed between the different antibody combinations.

Conclusions: The CD9/CD11b/HLA-DR antibody combination displays high sensitivity and specificity and can be used to diagnose APL.
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http://dx.doi.org/10.1111/ijlh.12929DOI Listing
April 2019

Evaluation of NCAM and c-Kit as hepatic progenitor cell markers for intrahepatic cholangiocarcinomas.

Pathol Res Pract 2018 Dec 13;214(12):2011-2017. Epub 2018 Sep 13.

Department of Pathology, Affiliated Tumor Hospital of Shanxi Medical University, Taiyuan, China. Electronic address:

Background: Intrahepatic cholangiocarcinomas (ICCs) are primary liver malignancies and are the second most common type of malignancy after hepatocellular carcinoma. ICCs are heterogeneous in clinical features, genotype, and biological behavior, suggesting that ICCs can initiate in different cell lineages.

Aim: We investigated intrahepatic cholangiocarcinoma RBE cell lines for the markers neural cell adhesion molecule (NCAM) and c-Kit, which possess hepatic progenitor cells properties.

Methods: NCAM + c-Kit + cells were tested for hepatic progenitor cell properties including proliferation ability, colony formation, spheroid formation, and invasiveness in NOD/SCID mice. The Agilent Whole Human Genome Microarray Kit was used to evaluate differences in gene expression related to stem cell signaling pathways between NCAM + c-Kit + and NCAM-c-Kit- subset cells. Microarray results were further confirmed by real-time RT-PCR.

Results: NCAM + c-Kit + cells showed hepatic progenitor cell-like traits including the abilities to self-renew and differentiate and tumorigenicity in NOD/SCID mice. Differences were observed in the expression of 421 genes related to stem cell signaling pathways (fc ≥ 2 or fc ≤ 0.5), among which 231 genes were upregulated and 190 genes were downregulated.

Conclusion: NCAM + c-Kit + subset cells in RBE may have properties of hepatic progenitor cells. NCAM combined with c-Kit may be a valuable marker for isolating and purifying ICC stem/progenitor cells.
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http://dx.doi.org/10.1016/j.prp.2018.09.005DOI Listing
December 2018

Clinical significance of droplet digital PCR quantitative monitoring of KIT gene mutation levels in core binding factor leukemia.

Int J Lab Hematol 2018 Dec 8;40(6):e124-e126. Epub 2018 Jul 8.

Department of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.

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http://dx.doi.org/10.1111/ijlh.12883DOI Listing
December 2018

Monitoring of clonal evolution of double C-KIT exon 17 mutations by Droplet Digital PCR in patients with core-binding factor acute myeloid leukemia.

Leuk Res 2018 06 22;69:89-93. Epub 2018 Apr 22.

Department of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan, PR China. Electronic address:

C-KIT gene mutations result in the constitutive activation of tyrosine kinase activity, and greatly affect the pathogenesis and prognosis of core-binding factor acute myeloid leukemia (CBF-AML). C-KIT mutations are often found as single point mutations. However, the rate of double mutations has recently increased in AML patients. In this study, we detected six cases (18.8%) harboring double C-KIT exon17 mutations in 75 patients with CBF-AML. The clone composition and dynamic evolution were analyzed by sequencing and droplet digital PCR (ddPCR). Results revealed that these double mutations can be occurred in either the same or different clones. Different clones of double mutations may result in different sensitivity to the treatment of CBF-AML. The clones with N822 mutation responded better to treatment as compared to those with D816 mutation. Moreover, D816 clone was readily transformed into a predominant clone at relapse. Meanwhile, the predominant clones in the same patient may change during the progression of disease. The emerging mutation can originate from a small quantity of clones at diagnosis or newly acquired during the course of disease. Furthermore, patients with double mutations had better overall survival (OS) and event-free survival (EFS) than those with single mutation, but the differences did not reach statistical significance (P > 0.05). The ddPCR is an effective method for monitoring clonal evolution in patients with CBF-AML.
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http://dx.doi.org/10.1016/j.leukres.2018.04.013DOI Listing
June 2018

Antimicrobial susceptibility and MIC distribution of 41 drugs against clinical isolates from China and reference strains of nontuberculous mycobacteria.

Int J Antimicrob Agents 2017 Mar 21;49(3):364-374. Epub 2016 Dec 21.

State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China. Electronic address:

To treat nontuberculous mycobacteria (NTM) infections more optimally, further research pertaining to mycobacterial susceptibility to antimicrobial agents is required. A total of 82 species of NTM reference strains and 23 species of NTM clinical isolates were included. Minimum inhibitory concentrations (MICs) for 41 drugs were determined using the microdilution method in cation-adjusted Mueller-Hinton broth. The results showed that most of the NTM were susceptible to aminoglycosides, quinolones, three macrolides (clarithromycin, azithromycin and roxithromycin), cefmetazole, linezolid and capreomycin. Rapidly growing mycobacterium strains were additionally susceptible to cefoxitin, clofazimine, rifapentine, doxycycline, minocycline, tigecycline, meropenem and sulfamethoxazole, whereas slowly growing mycobacterium strains were additionally susceptible to rifabutin. This study on the susceptibility of NTM includes the largest sample size of Chinese clinical isolates and reference strains. NTM species-specific drug susceptibility patterns suggested that it is urgent to identify the species of NTM, to normalise the treatment of NTM infectious disease and to clarify the resistance mechanisms of NTM.
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http://dx.doi.org/10.1016/j.ijantimicag.2016.10.024DOI Listing
March 2017

Detection of PML/RARα Fusion Gene in Bone Marrow of Patients with Functionalized Graphene Oxide.

Clin Lab 2016 ;62(5):823-31

Background: Current diagnostic methods of acute promyelocytic leukemia (APL) have some inevitable shortcomings; therefore, further studies are needed to develop more effective diagnostic methods. We used functionalized graphene oxide (GO) to detect the promyelocytic leukemia/retinoic acid receptor, α fusion gene (PML/RARα fusion gene) in bone marrow of APL patients. This method was more convenient and time-saving, and we can obtain the detection results in 1 hour.

Methods: Our group consists of 36 cases, among them are 16 cases which are PML-RARα positive, 20 cases which are PML-RARα negative. Firstly, samples were fixed, drilled, and incubated with antibody CD45. Secondly, GO, fluorescent probes, and buffer liquid were added. One hour later, samples were washed with PBS (1 x) buffer, centrifuged, and fluorescent signals were detected with flow cytometry.

Results: Using functional GO to carry the fluorescent probe we ascertained whether bone marrow samples contain the L type PML/RARα fusion gene. Using the probe, only cells which contain L type PML/RARα fusion gene will have fluorescent signals compared to no signals (p < 0.05). The GO detection method was accurate and has clinical diagnostic values (p < 0.05).

Conclusions: The GO detection method has the advantages of accurate, time-saving, energy-saving simple operation, and no pollution.
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http://dx.doi.org/10.7754/clin.lab.2015.150819DOI Listing
July 2016

Frequencies, Laboratory Features, and Granulocyte Activation in Chinese Patients with CALR-Mutated Myeloproliferative Neoplasms.

PLoS One 2015 16;10(9):e0138250. Epub 2015 Sep 16.

Institute of Hematology, the Second Hospital of Shanxi Medical University, Taiyuan, China.

Somatic mutations in the CALR gene have been recently identified as acquired alterations in myeloproliferative neoplasms (MPNs). In this study, we evaluated mutation frequencies, laboratory features, and granulocyte activation in Chinese patients with MPNs. A combination of qualitative allele-specific polymerase chain reaction and Sanger sequencing was used to detect three driver mutations (i.e., CALR, JAK2V617F, and MPL). CALR mutations were identified in 8.4% of cases with essential thrombocythemia (ET) and 5.3% of cases with primary myelofibrosis (PMF). Moreover, 25% of polycythemia vera, 29.5% of ET, and 48.1% of PMF were negative for all three mutations (JAK2V617F, MPL, and CALR). Compared with those patients with JAK2V617F mutation, CALR-mutated ET patients displayed unique hematological phenotypes, including higher platelet counts, and lower leukocyte counts and hemoglobin levels. Significant differences were not found between Chinese PMF patients with mutants CALR and JAK2V617F in terms of laboratory features. Interestingly, patients with CALR mutations showed markedly decreased levels of leukocyte alkaline phosphatase (LAP) expression, whereas those with JAK2V617F mutation presented with elevated levels. Overall, a lower mutant rate of CALR gene and a higher triple-negative rate were identified in the cohort of Chinese patients with MPNs. This result indicates that an undiscovered mutant gene may have a significant role in these patients. Moreover, these pathological features further imply that the disease biology varies considerably between mutants CALR and JAK2V617F.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0138250PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4574314PMC
June 2016

[Identification of a novel aberrant spliceosome of MPL gene (MPLL391-V392ins12)in patients with myeloproliferative neoplasms].

Zhonghua Xue Ye Xue Za Zhi 2015 Jul;36(7):559-62

Department of Hematology, the Second Hospital of Shanxi Medical University, Taiyuan 030001, China.

Objective: To identify the MPL L391-V392ins12 spliceosome and analyze its frequencies in patients with myeloproliferative neoplasms (MPN).

Methods: MPL aberrant spliceosome was identified through reverse transcription polymerase chain reaction (RT-PCR)combined with cloning sequencing. The mutation of this spliceosome in 248 MPN patients and 200 normal people was determined by allele-specific polymerase chain reaction (AS-PCR).

Results: A novel aberrant spliceosome of MPL gene (MPL L391-V392ins12)was identified, i.e. 36 bp intron was retained between exon7 and exon8, and there were 12 amino acids (EGLKLLPADIPV)inserted. MPL L391-V392ins12 mutation was detected in 19 (7.66%)of the 248 patients with MPN, including 1 (1.92%) of 52 patients with PV, 14 (9.66%) of 145 with ET, and 4 (7.84%) of 51 with PMF. And the mutation was not detected in the group of 200 normal people.

Conclusion: MPL L391-V392ins12 spliceosome is an aberrant spliceosome present in the MPN. It can be detected in PV, ET and PMF, and more frequently in ET and PMF. This mutation may play an important role in the process of MPN.
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http://dx.doi.org/10.3760/cma.j.issn.0253-2727.2015.07.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7342650PMC
July 2015

MDM4 overexpressed in acute myeloid leukemia patients with complex karyotype and wild-type TP53.

PLoS One 2014 18;9(11):e113088. Epub 2014 Nov 18.

Department of Hematology, the Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, P.R. China.

Acute myeloid leukemia patients with complex karyotype (CK-AML) account for approximately 10-15% of adult AML cases, and are often associated with a poor prognosis. Except for about 70% of CK-AML patients with biallelic inactivation of TP53, the leukemogenic mechanism in the nearly 30% of CK-AML patients with wild-type TP53 has remained elusive. In this study, 15 cases with complex karyotype and wild-type TP53 were screened out of 140 de novo AML patients and the expression levels of MDM4, a main negative regulator of p53-signaling pathway, were detected. We ruled out mutations in genes associated with a poor prognosis of CK-AML, including RUNX1 or FLT3-ITD. The mRNA expression levels of the full-length of MDM4 (MDM4FL) and short isoform MDM4 (MDM4S) were elevated in CK-AML relative to normal karyotype AML (NK-AML) patients. We also explored the impact of MDM4 overexpression on the cell cycle, cell proliferation and the spindle checkpoint of HepG2 cells, which is a human cancer cell line with normal MDM4 and TP53 expression. The mitotic index and the expression of p21, BubR1 and Securin were all reduced following Nocodazole treatment. Moreover, karyotype analysis showed that MDM4 overexpression might lead to aneuploidy or polyploidy. These results suggest that MDM4 overexpression is related to CK-AML with wild-type TP53 and might play a pathogenic role by inhibiting p53-signal pathway.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0113088PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4236138PMC
April 2016

Glycan imaging in intact rat hearts and glycoproteomic analysis reveal the upregulation of sialylation during cardiac hypertrophy.

J Am Chem Soc 2014 Dec 14;136(50):17468-76. Epub 2014 Oct 14.

Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, ‡State Key Laboratory of Biomembrane and Membrane Biotechnology, College of Life Sciences, §Synthetic and Functional Biomolecules Center, and ∥Peking-Tsinghua Center for Life Sciences, Peking University , Beijing 100871, China.

In the heart, glycosylation is involved in a variety of physiological and pathological processes. Cardiac glycosylation is dynamically regulated, which remains challenging to monitor in vivo. Here we describe a chemical approach for analyzing the dynamic cardiac glycome by metabolically labeling the cardiac glycans with azidosugars in living rats. The azides, serving as a chemical reporter, are chemoselectively conjugated with fluorophores using copper-free click chemistry for glycan imaging; derivatizing azides with affinity tags allows enrichment and proteomic identification of glycosylated cardiac proteins. We demonstrated this methodology by visualization of the cardiac sialylated glycans in intact hearts and identification of more than 200 cardiac proteins modified with sialic acids. We further applied this methodology to investigate the sialylation in hypertrophic hearts. The imaging results revealed an increase of sialic acid biosynthesis upon the induction of cardiac hypertrophy. Quantitative proteomic analysis identified multiple sialylated proteins including neural cell adhesion molecule 1, T-kininogens, and α2-macroglobulin that were upregulated during hypertrophy. The methodology may be further extended to other types of glycosylation, as exemplified by the mucin-type O-linked glycosylation. Our results highlight the applications of metabolic glycan labeling coupled with bioorthogonal chemistry in probing the biosynthesis and function of cardiac glycome during pathophysiological responses.
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http://dx.doi.org/10.1021/ja508484cDOI Listing
December 2014

Detection of promyelocytic leukemia/retinoic acid receptor α (PML/RARα) fusion gene with functionalized graphene oxide.

Int J Mol Sci 2013 Jun 20;14(6):12863-72. Epub 2013 Jun 20.

Department of Hematology, the Second Hospital of Shanxi Medical University, Taiyuan 030001, China.

An attempt was made to use functionalized graphene oxide (GO) to detect the Promyelocytic leukemia/Retinoic acid receptor α fusion gene (PML/RARα fusion gene), a marker gene of acute promyelocytic leukemia. The functionalized GO was prepared by chemical exfoliation method, followed by a polyethylene glycol grafting. It is found that the functionalized GO can selectively adsorb the fluorescein isothiocyanate (FITC)-labeled single-stranded DNA probe and quench its fluorescence. The probe can be displaced by the PML/RARα fusion gene to restore the fluorescence, which can be detected by laser confocal microscopy and flow cytometry. These can be used to detect the presence of the PML/RARα fusion gene. This detection method is verified to be fast, simple and reliable.
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http://dx.doi.org/10.3390/ijms140612863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3709817PMC
June 2013

Bifunctional unnatural sialic acids for dual metabolic labeling of cell-surface sialylated glycans.

J Am Chem Soc 2013 Jun 14;135(25):9244-7. Epub 2013 Jun 14.

Shenzhen Graduate School of Peking University, Shenzhen 518055, China.

Sialic acid analogues containing a unique chemical functionality or chemical reporter have been metabolically incorporated into sialylated glycans. This process, termed metabolic glycan labeling, has emerged as a powerful tool for studying sialylation as well as other types of glycosylation. Currently, this technique can install only a single functionality. Here we describe a strategy for dual labeling of sialylated glycans using a new class of bifunctional sialic acid analogues containing two distinct chemical reporters at the N-acyl and C9 positions. These bifunctional unnatural sialic acids were metabolically incorporated into cellular glycans, where the two chemical reporters exerted their distinct functions. This approach expands the capability of metabolic glycan labeling to probe sialylation and glycan-protein interactions.
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http://dx.doi.org/10.1021/ja402326zDOI Listing
June 2013

The short isoform of the long-type PML-RARA fusion gene in acute promyelocytic leukaemia lacks sensitivity to all-trans-retinoic acid.

Br J Haematol 2013 Jul 30;162(1):93-7. Epub 2013 Apr 30.

Department of Hematology, Second Hospital of Shanxi Medical University, 382 Wuyi Road, Taiyuan, China.

Alternative splicing is associated with human disease. In acute promyelocytic leukaemia (APL) patients with the long (L)-type promyelocytic leukaemia-retinoic acid receptor α fusion gene (PML-RARA), three alternative splicing isoforms can be detected: E5(+)E6(+), E5(-)E6(+), and E5(-)E6(-). This study is the first to demonstrate that alternative splicing of L-type PML-RARA is associated with time to achieve complete remission (CR) in APL. Higher expression of the E5(-)E6(-) isoform, the short isoform, was related to longer time to achieve CR. Each isoform was constructed into recombinant lentiviral vector and transfected into U937 cells. Compared with the E5(-)E6(+) and E5(+)E6(+) groups, the U937 cells with E5(-)E6(-) showed lower sensitivity to all-trans-retinoic acid treatment.
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http://dx.doi.org/10.1111/bjh.12362DOI Listing
July 2013

A tetraploid minimally differentiated acute myeloblastic leukemia with extensive erythrophagocytosis: a case report and literature review.

Int J Hematol 2012 Dec 28;96(6):801-5. Epub 2012 Sep 28.

Institute of Hematology, The Second Hospital of Shanxi Medical University, 382 Wuyi Road, Taiyuan, 030001, Shanxi, People's Republic of China.

Tetraploidy is a rare chromosome number aberration in de novo acute myeloid leukemia (AML), and may be associated with erythrophagocytosis by leukemic blast cells. We report a 48-year-old female patient with minimally differentiated acute myeloblastic leukemia (AML-M0) exhibiting tetraploidy and erythrophagocytosis. The karyotype was 46,XX[2]/92,XXXX[18]. Bone marrow aspirate smears showed large and prominent nuclei, with erythrophagocytosis in leukemic cells. Fluorescence in situ hybridization using RUNX1 dual color break probes detected four fusion signals, accounting for 95 % (190/200), in one interphase nucleus. The mutations of TP53 and the fusion genes RUNX1/ETO, CBFβ/MYH11, and PML/RARα were all negative. This patient showed a poor response to chemotherapy, and died 66 days after the onset. To our knowledge, this is the first reported case of AML-M0 with tetraploidy and erythrophagocytosis and without additional chromosome aberrations. This case of tetraploid AML with poor prognosis suggests that further biological study of more cases of tetraploid AML will be of great importance in improving the understanding and prognosis of this tetraploid AML.
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http://dx.doi.org/10.1007/s12185-012-1179-6DOI Listing
December 2012

Acute lymphoblastic leukemia expressing b3a2 (p210), e1a2 (p190), and variant e1a2 BCR-ABL transcripts: a case report and review of the literature.

Acta Haematol 2012 30;128(2):119-23. Epub 2012 Jun 30.

Institute of Hematology, Second Hospital of Shanxi Medical University, Taiyuan, PR China.

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http://dx.doi.org/10.1159/000338261DOI Listing
October 2012

The PML gene of the PML-RARα V-form fusion transcript breaks within exon 6.

Acta Haematol 2011 20;126(4):216-9. Epub 2011 Sep 20.

Department of Hematology, Second Hospital of Shanxi Medical University, 382 Wuyi Road, Taiyuan, China.

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http://dx.doi.org/10.1159/000329898DOI Listing
January 2012

Detection of MPL exon10 mutations in 103 Chinese patients with JAK2V617F-negative myeloproliferative neoplasms.

Blood Cells Mol Dis 2011 Jun 8;47(1):67-71. Epub 2011 May 8.

Institute of Hematology, the Second Hospital of Shanxi Medical University, 382 Wuyi Road, Taiyuan, China.

JAK2V617F mutation has been reported in 90% of patients with polycythemia vera (PV) and about 50% of patients with essential thromobocythemia (ET) and primary myelofibrosis (PMF). Recently, acquired mutations in the transmembrane-juxtamembrane region of MPL (MPLW515 mutations) have been reported in approximately 5% of JAK2V617F-negative PMF and about 1% of all cases of ET. MPL is the receptor for thrombopoietin that regulates the production of platelets by bone marrow. It is likely that some mutations more closely related to ET in MPL exon10 may have been missed by current assays. We inferred that there might be other mutations in MPL exon10 for MPN patients in addition to MPLW515 mutations. To investigate its mutation types and prevalence in Chinese patients with myeloproliferative neoplasms (MPN), we performed mutation detection on MPL exon10 in 103 JAK2V617F-negative MPN patients by single strand conformation polymorphism (SSCP) and allele-specific PCR (AS-PCR) combined with sequencing. As a result, one previously unrecognized MPL mutation (12-bp in-frame insertion) was identified in one patient with ET in addition to an MPLW515K mutation identified in one PMF patient. This confirms our hypothesis that BCR/ABL negative and JAK2V617F-negative MPN patients have other mutations besides W515 mutation in MPL exon10 and mutations other than single nucleotide exchange also exist. In addition, MPL mutation was associated with Chinese MPN patients.
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http://dx.doi.org/10.1016/j.bcmd.2011.04.004DOI Listing
June 2011
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