The prognostic impact of lymphocyte subsets in newly diagnosed acute myeloid leukemia

Park, Yumi; Lim, Jinsook; Kim, Seonyoung; Song, Ik‐Chan; Kwon, Kyechul; Koo, Sunhoe; Kim, Jimyung

doi:10.5045/br.2018.53.3.198

Cited by 10 publications

(4 citation statements)

References 26 publications

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“…The immune system plays an important role in eliminating malignant cells through immune surveillance (46). Several studies have reported abnormal changes in the relative frequency and function of lymphocytes, especially T cells, in AML (47,48). CAR-T cells can specifically kill tumor cells without the limitations of major histocompatibility complex.…”

Section: Discussionmentioning

confidence: 99%

Cytotoxic effect of CLL‑1 CAR‑T cell immunotherapy with PD‑1 silencing on relapsed/refractory acute myeloid leukemia

Lin

Zhang

et al. 2021

Mol Med Rep

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The activation of chimeric antigen receptor (CAR)-T cells can lead to persistently high levels of programmed cell death 1 (PD-1) antigen and eventually causes the exhaustion of T cells. The effectiveness of CAR-T cells targeting C-type lectin-like molecule-1 (CLL-1) combined with PD-1 silencing therapy for acute myeloid leukemia (AML) was evaluated in the present study. CLL-1 levels in primary AML bone marrow samples was examined using flow cytometric analysis. We designed a CLL-1 CAR-T, containing CLL-1-specific single-chain variable fragment, CD28, OX40, CD8 hinge and TM and CD3-ζ signaling domains. CLL-1 CAR-T with PD-1 silencing was constructed. It was confirmed that CLL-1 is expressed on the surface of AML cells. CLL-1 CAR-T showed specific lysing activity against CLL-1 + AML cells. PD-1 silencing enhanced the killing ability of CLL-1 CAR-T. Furthermore, it was found that CAR-T derived from healthy donor T cells was more effective in killing THP-1 cells (a human acute monocytic leukemia cell line) than those from patient-derived T cells. These results indicated that CLL-1 CAR-T and PD-1 knockdown CLL-1 CAR-T could be used as a potential immunotherapy to treat relapsed or refractory AML.

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Section: Discussionmentioning

confidence: 99%

Cytotoxic effect of CLL‑1 CAR‑T cell immunotherapy with PD‑1 silencing on relapsed/refractory acute myeloid leukemia

Lin

Zhang

et al. 2021

Mol Med Rep

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“…For instance, CD8 + T cells could effectively restore T cell function and improve their antitumor activity by inhibiting ferroptosis (Ma et al, 2021). Moreover, there is emerging evidence that a high proportion of natural killer (NK) cells is associated with death before remission (Park et al, 2018). However, the degree to which ferroptosis influences survival and treatment strategy of AML remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Identification and Validation of a Prognostic Risk-Scoring Model Based on Ferroptosis-Associated Cluster in Acute Myeloid Leukemia

Wang

Zhuo

Wang

et al. 2022

Front. Cell Dev. Biol.

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Background: Emerging evidence has proven that ferroptosis plays an important role in the development of acute myeloid leukemia (AML), whereas the exact role of ferroptosis-associated genes in AML patients’ prognosis remained unclear.Materials and Methods: Gene expression profiles and corresponding clinical information of AML cases were obtained from the TCGA (TCGA-LAML), GEO (GSE71014), and TARGET databases (TARGET-AML). Patients in the TCGA cohort were well-grouped into two clusters based on ferroptosis-related genes, and differentially expressed genes were screened between the two clusters. Univariate Cox and LASSO regression analyses were applied to select prognosis-related genes for the construction of a prognostic risk-scoring model. Survival analysis was analyzed by Kaplan–Meier and receiver operator characteristic curves. Furthermore, we explored the correlation of the prognostic risk-scoring model with immune infiltration and chemotherapy response. Risk gene expression level was detected by quantitative reverse transcription polymerase chain reaction.Results: Eighteen signature genes, including ZSCAN4, ASTN1, CCL23, DLL3, EFNB3, FAM155B, FOXL1, HMX2, HRASLS, LGALS1, LHX6, MXRA5, PCDHB12, PRINS, TMEM56, TWIST1, ZFPM2, and ZNF560, were developed to construct a prognostic risk-scoring model. AML patients could be grouped into high- and low-risk groups, and low-risk patients showed better survival than high-risk patients. Area under the curve values of 1, 3, and 5 years were 0.81, 0.827, and 0.786 in the training set, respectively, indicating a good predictive efficacy. In addition, age and risk score were the independent prognostic factors after univariate and multivariate Cox regression analyses. A nomogram containing clinical factors and prognostic risk-scoring model was constructed to better estimate individual survival. Further analyses demonstrated that risk score was associated with the immune infiltration and response to chemotherapy. Our experiment data revealed that LGALS1 and TMEM56 showed notably decreased expression in AML samples than that of the normal samples.Conclusion: Our study shows that the prognostic risk-scoring model and key risk gene may provide potential prognostic biomarkers and therapeutic option for AML patients.

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“…High white blood cell (WBC) index is a prognostic factor for AML [9]. High percentages of CD19+ B cells in newly diagnosed AML patients were reported to be unrelated to DFS and OS [10]. However, it has been reported that the transitional B cell frequency of patients with AML was higher than that of healthy controls, and patients sampled further from the end of chemotherapy had lower transitional B cell frequency [11].…”

Section: Introductionmentioning

confidence: 99%

The Role of Regulatory B Cells in Patients with Acute Myeloid Leukemia

Wang

Liu

2019

Med Sci Monit

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Background Regulatory B (Breg) cells are a group of B cells with immunomodulatory function, which mainly exert negative immunomodulatory function by secreting IL-10 and other cytokines. Due to their immunoregulatory properties, Breg cells may participate in the pathogenesis of acute myeloid leukemia (AML). This study was designed to explore the frequency of Breg cells and the relationship between the Breg cells and clinical data in patients with AML. Material/Methods A total of 46 (36 in peripheral blood, 10 in bone marrow) AML patients and 15 healthy donors (HD) were included for detection of Breg cells frequency by multicolor flow cytometry. All cases were divided into different groups according to FAB subtypes of leukemia, white blood cell count (WBC) levels, age, cytogenetic characteristics, and molecular abnormalities, and were compared the differences of Breg cell frequency. Survival curve analysis was performed to estimate the value of Breg cell frequency in prognosis among cases with AML. Results We found that the frequency of Breg cells was higher in AML patients both in peripheral blood (PB) and in bone marrow (BM) compared with those in HDs. The AML patients with high WBC levels had higher Breg cell frequency compared with those with low WBC levels. Low-risk patients with had lower Breg cells frequency compared to the medium-risk patients. The patients with high WBC and high Breg cells frequency showed a shorter overall survival. Similarly, the overall survival of AML patients in the older group with high Breg cells frequency was significantly shorter than in the younger group with low Breg cell frequency. Conclusions For AML patients, the frequency of Breg cells was elevated, and high frequency of Breg cells may reveal poor prognosis.

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The prognostic impact of lymphocyte subsets in newly diagnosed acute myeloid leukemia

Cited by 10 publications

References 26 publications

Cytotoxic effect of CLL‑1 CAR‑T cell immunotherapy with PD‑1 silencing on relapsed/refractory acute myeloid leukemia

Cytotoxic effect of CLL‑1 CAR‑T cell immunotherapy with PD‑1 silencing on relapsed/refractory acute myeloid leukemia

Identification and Validation of a Prognostic Risk-Scoring Model Based on Ferroptosis-Associated Cluster in Acute Myeloid Leukemia

The Role of Regulatory B Cells in Patients with Acute Myeloid Leukemia

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