New approaches in allogenic transplantation in AML

Pei, Xu‐Ying; Huang, Xiao‐Jun

doi:10.1053/j.seminhematol.2018.08.007

Cited by 11 publications

(6 citation statements)

References 104 publications

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“…Conventional chemotherapeutic approaches, as the mainstay for AML treatment, usually brings CR in these patients of the intermediate-risk and the high-risk group but can fail in long-term leukemia control due to the high incidence of subsequent relapse (Cornelissen and Blaise, 2016 ). Allo-HSCT, which offers a strong GVL effect, is generally recommended as a post-remission therapy for AML patients who are eligible candidates (Cornelissen and Blaise, 2016 ; Pei and Huang, 2019 ). Results from previous studies suggested that allo-HSCT offers a significant advantage with regard to RFS and OS compared with that of chemotherapy or autologous transplantation particularly.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic Therapy Promotes the Ratio of Th1/Th17 Lineage to Reverse Immune Evasion and Treat Leukemia Relapse Post-allogeneic Stem Cell Transplantation in Non-APL AML Patients

Dai

et al. 2021

Front. Mol. Biosci.

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To reverse the early-stage relapse post-hematopoietic stem cell transplantation, we investigated the safety and efficacy of a new epigenetic regimen (chidamide and decitabine plus thymalfasin simultaneously) on acute myeloid leukemia patients (excluding acute promyelocytic leukemia). Twenty-four patients were enrolled in this observational study during April 2015 to May 2018. The most common adverse event was reversible CTCAE grade 2 thrombocytopenia (20/24). Strikingly, all 24 patients had response to this epigenetic regimen accompanied with decreased measurable residual disease. The overall survival rate is 79.2% (19/24), with a relapse-free survival rate of 79.2% (19/24). During this regimen treatment, Th1 cells and CD3+CD4-CD8+T cells increased, and Th17 cells decreased gradually. The status of high Th1 and low Th17 cells was still observed on the 3rd month after discontinuation of this regimen. Interestingly, the significantly elevated ratio of Th1/Th17 seemed to reflect the treatment-related immune effect, which may be a valuable marker to be monitored in the early-relapse stage for evaluating the efficacy and prognosis.

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Section: Discussionmentioning

confidence: 99%

Epigenetic Therapy Promotes the Ratio of Th1/Th17 Lineage to Reverse Immune Evasion and Treat Leukemia Relapse Post-allogeneic Stem Cell Transplantation in Non-APL AML Patients

Dai

et al. 2021

Front. Mol. Biosci.

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“…1,3 It is one of the most common and severe types of acute leukemia in adults, 2 with high incidence and mortality rates. 4,5 AML is a destructive malignancy with disruptions in oncogenes/tumor suppressor genes and limited treatment options, urgently necessitating new therapeutic approaches. [6][7][8] Despite the general belief that relapsed AML is potentially curable, the reality is that the prognosis for patients with relapsed AML is extremely poor, with only a small percentage achieving remission.…”

Section: Introductionmentioning

confidence: 99%

To study the diagnostic and prognostic value of GADD45α in AML based on bioinformatics and its preliminary experimental validation

Gui,

Zhang,

Tong

et al. 2023

Preprint

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Objectives Exploring the expression status, prognostic value, immune infiltration, potential functions, and mechanisms of GADD45α in AML using bioinformatics. Methods Using the GEPIA2 database to analyze the expression levels of GADD45α in AML and other cancers, and to assess the correlation between GADD45α levels and prognosis in AML. Conducting immune regulation gene analysis, immune checkpoint analysis, and immune infiltration analysis of GADD45α in AML in Sangerbox. Obtaining the protein interaction network with GADD45α from the STRING database and conducting GO and KEGG analysis in Sangerbox. By establishing stable overexpression of GADD45α in AML cells, using CCK-8 and Annexin V-FITC/APC to respectively detect the effects of overexpression and knockdown of GADD45α on cell proliferation and apoptosis in AML cells. Validating the diagnostic and prognostic value of GADD45α in AML. All data were statistically analyzed using SPSS 23.0 software. Results GADD45α is mostly downregulated in cancer, and is downregulated in AML, which is associated with poor prognosis. We found significant correlation between GADD45α and immune cells in AML in Sangerbox. We also found that GADD45α expression in AML is closely related to 43 checkpoints, including VEGFB, ARG1, KIR2DL1, KIR2DL3, TIGIT, and is closely related to five types of immune cells, including chemokines, receptors, MHC, immune inhibitors, and immune stimulators. This indicates that GADD45α may coordinate the activity of these ICP genes in different signaling pathways and may become an ideal immunotherapy target. We found that GADD45α interacts with TDG, FOXO3, TP53, CDKN1A, CDK1, AURKA, CCNB1, PCNA, MAP2K6, and MAP3K4 proteins, and after GO and KEGG analysis, we found that its biological function may be involved in cell cycle arrest, mitotic G1/S checkpoint, and other processes. KEGG enrichment of GADD45α is related to cell senescence, cell cycle, p53 signaling pathway, and FoxO signaling pathway. Overexpression of GADD45α can inhibit the proliferation of leukemia cells, promote apoptosis, and after GADD45α knockdown, it can promote the proliferation of leukemia cells and inhibit apoptosis. Conclusions GADD45α is a prognostic marker for AML, and its expression levels are associated with various immune cell molecules, immune checkpoints, and immune regulatory genes. Detecting GADD45α levels helps predict the prognosis of AML, providing a new method for optimizing and monitoring the effectiveness of anti-AML immunotherapy. Further validation of the GADD45α signaling pathway is more conducive to the discovery of occurrence and development mechanisms, and is more beneficial for patient treatment.

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“…The median age at diagnosis is 67 years [ 1 ], with half of patients diagnosed at 70 years or older [ 2 ]. Over the past decades, the outcomes of transplantation and some targeted therapeutics have progressed significantly beyond those of conventional chemotherapy [ 3 , 4 ]. However, the 5-year overall survival (OS) rate remains at 30% and at only 10% for older patients [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Circular RNA PVT1 Regulates Cell Proliferation, Migration, and Apoptosis by Stabilizing c-Myc and Downstream Target CXCR4 Expression in Acute Myeloid Leukemia

Sheng¹,

Hong²,

Li³

et al. 2023

Tjh

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Objective: This study aimed to investigate the role and mechanism of circular RNA PVT1 (circPVT1) in patients with acute myeloid leukemia (AML). Materials and Methods: The expression of circPVT1 in 23 patients with de novo AML (not acute promyelocytic leukemia, not APL) and cell lines were detected by RT-qPCR. Loss of function assays were carried out to explore the influence of silenced circPVT1 on the proliferation, migration, and apoptosis in the THP-1 cell line. CCK-8 assays, trans-well assays, and annexin V/PI staining assays were performed to assess proliferation, migration, and apoptosis, respectively. Results: CircPVT1 was highly expressed in AML patients and myeloid cell lines compared to healthy controls. Higher expression of circPVT1 was related to shorter overall survival (OS) and relapse-free survival (RFS) in AML patients. Cell viability and migration were inhibited and apoptosis was increased when circPVT1 was knocked down in THP-1 cells. Knockdown of circPVT1 resulted in marked suppression of c-Myc protein with no significant change in mRNA levels. We also found that circPVT1 knockdown markedly increased the phosphorylation of c-Myc Thr-58, which was responsible for c-Myc degradation. Silencing of c-Myc caused a significant decrease in CXCR4 mRNA and protein expression, whereas the overexpression of c-Myc caused the opposite result, suggesting that CXCR4 is a target molecule of c-Myc. Finally, we found that overexpression of c-Myc could partially reverse circPVT1 knockdown-induced anti-tumor effects on THP-1 cells in vitro. Conclusion: Our findings showed that circPVT1 was highly expressed in AML patients and was related to shorter OS and RFS. CircPVT1 may exert an oncogenic effect in THP-1 cells by stabilizing c-Myc protein expression and downstream target CXCR4 expression. These data indicate that circPVT1 may be a promising therapeutic target for AML.

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New approaches in allogenic transplantation in AML

Cited by 11 publications

References 104 publications

Epigenetic Therapy Promotes the Ratio of Th1/Th17 Lineage to Reverse Immune Evasion and Treat Leukemia Relapse Post-allogeneic Stem Cell Transplantation in Non-APL AML Patients

Epigenetic Therapy Promotes the Ratio of Th1/Th17 Lineage to Reverse Immune Evasion and Treat Leukemia Relapse Post-allogeneic Stem Cell Transplantation in Non-APL AML Patients

To study the diagnostic and prognostic value of GADD45α in AML based on bioinformatics and its preliminary experimental validation

Circular RNA PVT1 Regulates Cell Proliferation, Migration, and Apoptosis by Stabilizing c-Myc and Downstream Target CXCR4 Expression in Acute Myeloid Leukemia

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