Publications by authors named "JianMei Chang"

13 Publications

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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

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

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

Myelodysplastic Syndrome with t(1;14),t(1;17),t(1;19) Transforms to AML-M5: A Case Report and Literature Review.

Ann Clin Lab Sci 2020 May;50(3):401-403

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

Chromosomal aberrations play an important role in the incidence of myelodysplastic syndromes (MDS) and development to acute myeloid leukemia (AML). We report a case of a 62-year-old male patient diagnosed with MDS with excess blasts. The karyotype was 45, XY,+1,+1,-7,-10,-22,t(1;14) (q21;q32),t(1;17)(q21;p13),t(1;19)(q21;p13). The patient and his family refused treatment for financial reasons. After 2 months, the patient's MDS transformed into acute myeloid monocytic leukemia (AML-M5). This case of MDS with poor prognosis shows that patients with chromosomal numerical abnormality and balanced translocations should be treated early to prevent transition to AML. Further study of this case will reveal the molecular mechanism of MDS-to-AML transformation and identify new leukemic fusion genes.
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May 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

T-cell blast crisis of chronic myelogenous leukemia presented with coexisting p210 and p190 BCR-ABL transcripts and t(10;11)(q11;p15).

J Clin Lab Anal 2020 Jun 13;34(6):e23241. Epub 2020 Feb 13.

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

Background: Blast transformation of chronic myelogenous leukemia (CML) to T lymphoblastic lymphoma/acute lymphoblastic leukemia (T-LBL/ALL) is rare, and the molecular mechanism is still unclear.

Case Report: A 28-year-old woman who developed T-ALL with coexpressing both p210 and p190 BCR-ABL transcripts five years after the initial diagnosis of CML in chronic phase. The proliferation of bone marrow was extremely active with blast cells over 20%. Chromosome analysis revealed t(9;22)(q34;q11) and t(10;11)(q25;p15). Flow immunophenotyping showed that blasts expressed CD4, CD7, CD11b, CD38, CD34, CD33, and cCD3.

Conclusion: It is the first T-cell blast of CML case with coexisting p210 and p190 as well as additional chromosome translocations. Through review this case and previous reports, we will reveal that CML patients with T-lymphocyte transformation depend on potential molecular and pathological mechanism.
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http://dx.doi.org/10.1002/jcla.23241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7307355PMC
June 2020

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

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

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
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