Publications by authors named "Ya-zhe Wang"

Compared to other immune checkpoint molecules, T cell immunoglobulin domain and mucin domain-3 (TIM-3) is highly expressed on natural killer (NK) cells, but its functional role and prognostic significance in acute myeloid leukemia (AML) remains unclear. This study aims to evaluate the role of TIM-3 expression on the cytotoxic and killing capacity of NK cells and its prognostic significance in AML. AML public single-cell RNA sequencing (scRNAseq) data were used to analyze the correlation of transcript levels between (encoding TIM-3) and cytotoxic molecules in NK cells.

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: The effect of the expression of the newly identified immune checkpoint, T cell immunoglobulin and immunoreceptor tyrosine-based inhibition motif domain (TIGIT) on NK cells in core binding factor-acute myeloid leukemia (CBF-AML) remains to be investigated. : Fresh bone marrow samples from a total of 39 newly diagnosed CBF-AML patients and 25 healthy donors (HDs) were collected for testing the phenotype and function state of total NK, CD56, and CD56 NK cell subsets after in vitro stimulation. : The frequencies of TIGIT cells in total NK, CD56, and CD56 NK cell subsets had no significant difference between patients and HDs.

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Article Synopsis
  • Chemotherapy is an effective treatment for acute myeloid leukemia (AML) but often leads to myelosuppression and poor recovery of blood cell production.
  • Dysfunction in bone marrow endothelial cells (ECs) is observed in AML patients, particularly those with inadequate hematopoietic reconstitution post-transplantation, making it essential to understand the mechanisms behind this dysfunction.
  • Elevated TGF-β signaling in ECs from AML patients causes damage that impairs hematopoiesis, but using TGF-β inhibitors has shown promise in restoring EC function and normal blood cell production without worsening AML.
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  • The study investigates the levels of soluble immune checkpoint molecules TIM-3, Gal-9, and CEACAM1 in the plasma of newly diagnosed adult patients with acute myeloid leukemia (AML) compared to healthy donors.
  • Results show that AML patients had higher levels of soluble TIM-3, which was identified as a significant independent factor predicting poor relapse-free survival (RFS) and event-free survival (EFS).
  • Additionally, elevated levels of soluble CEACAM1 and Gal-9 were associated with lower RFS, especially in patients undergoing allogeneic hematopoietic stem cell transplantation.
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  • T lymphocytes are crucial for fighting tumors, but research on their differentiation in acute myeloid leukemia (AML) patients, especially in the bone marrow, is limited compared to solid tumors.
  • A study of 103 AML patients showed higher levels of CD8 effector T cells compared to healthy donors, with variations based on genetic mutations affecting T-cell memory and differentiation profiles.
  • Low levels of certain T-cell subsets, specifically CD4 effector memory and CD8 naïve T cells, were linked to worse relapse-free and event-free survival outcomes in AML patients.
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Introduction: Central nervous system leukemia (CNSL) remains a serious complication in patients with acute myeloid leukemia (AML) and an ambiguous prognostic factor for those receiving allo-geneic hematopoiesis stem cell transplantation (allo-HSCT). It is unknown whether using more sensitive tools, such as multiparameter flow cytometry (MFC), to detect blasts in the cerebrospinal fluid (CSF) would have an impact on outcome.

Methods: We retrospectively analyzed the clinical outcomes of 1472 AML patients with or without cytology or MFC positivity in the CSF before transplantation.

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  • Thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF) are types of myeloproliferative neoplasms that are challenging to differentiate based on typical characteristics and genetic markers.
  • A study analyzed 211 patients with these conditions, revealing significant differences in blood cell types and specific gene expressions that could be used to distinguish PMF from ET and PV.
  • The use of flow cytometry, particularly certain immune cell markers, provided high sensitivity and specificity for diagnosing PMF and differentiating it from other conditions, indicating its potential to inform treatment decisions effectively.
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Introduction: Immune microenvironment plays an important role in the occurrence and development of acute myeloid leukemia (AML). Studies assessing the prognostic significance of bone marrow (BM) lymphocyte subsets' frequencies at diagnosis in patients with AML were limited.

Methods: Fresh BM samples collected from 97 adult AML patients at diagnosis were tested for lymphocyte, T, CD4 T, CD8 T, γδT, NK, and B cell frequencies using multi-parameter flow cytometry.

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  • Acute myeloid leukemia (AML) patients with the genetic marker t(8;21) show varying levels of interleukin 7 receptor (IL7R) expression, which can be classified into low-expressing (IL7R-L) and high-expressing (IL7R-H) groups.
  • Patients in the IL7R-L group have a significantly lower relapse-free survival (RFS) rate and a higher association with KIT mutations compared to IL7R-H patients.
  • A decrease in IL7R expression correlates with reduced activation and proliferation of T cells, indicating that low IL7R levels at diagnosis may serve as a prognostic factor for relapse risk in this specific AML subgroup.
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Background: ZNF384 rearrangement has been recently identified as a new subtype of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). However, comprehensive studies clarifying immunophenotypic features and discriminating them from non-ZNF384 in adult BCP-ALL remain scarce to date.

Methods: Flow cytometric assessments were retrospectively performed in 43 patients with ZNF384 rearrangement, 45 with BCR-ABL1, 29 with KMT2A rearrangement and 44 with other BCP-ALL in the analysis cohort.

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Background: Poor graft function (PGF) or prolonged isolated thrombocytopenia (PT), which are characterized by pancytopenia or thrombocytopenia, have become serious complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Our previous single-arm trial suggests that N-acetyl-L-cysteine (NAC) prophylaxis reduced PGF or PT after allo-HSCT. Therefore, an open-label, randomized, phase 3 trial was performed to investigate the efficacy and tolerability of NAC prophylaxis to reduce PGF or PT after allo-HSCT.

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Acute myeloid leukemia (AML) with t(8;21) is a heterogeneous disease and needs to be stratified. Both, cancer cells and immune cells participate in tumor initiation, growth and progression and might affect clinical outcomes. TIM-3 (T cell immunoglobulin and mucin domain-containing protein 3), an immune checkpoint molecule, is expressed not only on immune cells but also on leukemic stem cells (LSCs) in AML.

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Elderly individuals exhibit unbalanced bone marrow (BM) effector T cell subset differentiation, such as increased T helper type 1 (Th1) and T cytotoxic type 1 (Tc1) cell frequencies, but the underlying mechanism is still unclear. Endothelial cells (ECs), which are instructive components of the BM microenvironment, exhibit the phenotype of semi-professional antigen-presenting cells and regulate T cell recruitment and activation. Thus, we compared the frequency and function of BM ECs, especially their capacity to regulate effector T cell subsets, between young and elderly healthy individuals, and explored the underlying mechanism of this immunomodulatory discrepancy.

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We performed a retrospective analysis to investigate dynamic peri-hematopoietic stem cell transplantation (HSCT) minimal/measurable residual disease (MRD) on outcomes in patients with T-cell acute lymphoblastic leukemia (T-ALL). A total of 271 patients were enrolled and classified into three groups: unchanged negative MRD pre- and post-HSCT group (group A), post-MRD non-increase group (group B), and post-MRD increase group (group C). The patients in group B and group C experienced a higher cumulative incidence of relapse (CIR) (42% vs.

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Objective: To investigate the predict significance of the high aldehyde dehydrogenase activity (ALDH) propitiation to the relapse of t(8;21) acute myeloid leukemia(AML) patients before and after treatment.

Methods: Bone marrow samples of 23 t(8;21) AML patients diagnosis and achieved complete remission in our hospital from April 2015 to June 2016 were collected, then flow cytometry method was used to detect the activity of ALDH, relationship between it and relapse was analyzed.

Results: All the patients were followed up for a median of 32 (2-52) months.

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Purpose: The cancer-testis antigen, which is a preferentially expressed antigen of melanoma (PRAME), is an ideal target for immunotherapy and cancer vaccines. Since the expression of this antigen is relevant to therapy responses, the heterogeneity in its expression and the underlying mechanism need to be investigated.

Patients And Methods: Plasma cell sorting was performed in 48 newly diagnosed multiple myeloma (MM) patients.

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Many studies have confirmed that overexpressed WT1 exists in leukemic cells, especially in AML. However, the immunophenotypic features of this sort of leukemic cells remain to be unclarified. We retrospectively analyzed the immunophenotype of 283 newly diagnosed AML patients with intermediated and poor cytogenetic risk to evaluate the correlation between phenotype and WT1 overexpression.

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Article Synopsis
  • Acute myeloid leukemia (AML) with the t(8;21) mutation is varied and requires better risk assessment alongside monitoring minimal residual disease (MRD) indicated by RUNX1-RUNX1T1 levels.
  • A study of 66 AML patients revealed that certain cell populations, particularly those showing high aldehyde dehydrogenase (ALDH) activity, were linked to lower 2-year relapse-free survival rates.
  • Combining ALDH status at diagnosis with MRD information helps refine risk stratification, indicating that patients with high ALDH and poor MRD outcomes are at greater risk for relapse.
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  • - The study aimed to evaluate a flow cytometric scoring system for diagnosing myelodysplastic syndromes (MDS) by analyzing the cell types in 130 MDS patients compared to healthy and pathological controls.
  • - Results showed that a two-parameter scoring system outperformed both a four-parameter system and an erythroid scoring system, achieving a sensitivity of 76.1% and a specificity of 81.5% for low-risk MDS.
  • - Combining scoring systems improved sensitivity to 87.0%, but decreased specificity to 54.6%, suggesting that the two-parameter system alone is effective for accurate low-risk MDS diagnosis.
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This study evaluated the effects of pretransplantation minimal residual disease (pre-MRD) on outcomes of patients with acute lymphoblastic leukemia (ALL) who underwent unmanipulated haploidentical stem cell transplantation (haplo-SCT). A retrospective study including 543 patients with ALL was performed. MRD was determined using multiparametric flow cytometry.

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Background: Daunorubicin is a traditional chemotherapeutic agent that plays a pivotal role in leukemia therapy. However, the dose-related toxicity remains a considerable challenge. The apoptosis-regulating gene, , is downregulated in various tumors, including leukemias, and may provide a potential target for the diagnosis and treatment of leukemia.

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A seven-color panel was used to detect minimal residual disease (MRD) in T cell acute lymphoblastic leukemia (T-ALL) via flow cytometry (FCM). Its availability and clinical significance were studied in T-ALL patients with newly diagnosed (n = 64), relapsed (n = 48) and morphologically complete remission (n = 103). The following four features were used to identify immature cCD3+ T cells: CD34+, TdT+, but mCD3-/dim+, and CD45dim+.

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Objective: To preliminarily identify the existence of CD34 leukemia stem cell (LSC) in t(8;21) acute myeloid leukemia (AML) by in vitro test.

Methods: Bone marrow samples collected from newly diagnosed t(8;21) AML patients were tested. LinCD34 CD38(abbreviation, CD34CD38), LinCD34CD38 (abbreviation, CD34CD38) and LinCD34CD38CD45SSC(abbreviation, CD34"LSC") cell fractions were gated by flow cytometry after staining with fluorescent antibodies.

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Multiple myeloma (MM) patients commonly present abnormal expression of cancer-testis antigens, which may serve as immunotherapeutic targets and prognostic factors. We previously reported that preferentially expressed antigen of melanoma (PRAME) overexpression in bone marrow mononuclear cells is related to progression in MM patients treated with non-bortezomib-containing regimens. The mechanism underlying variations in PRAME expression remains unknown.

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