Genomic and transcriptomic profiles and <i>in vitro</i> resistance to mitoxantrone and idarubicin in pediatric acute leukemias

Laskowska, Joanna; Lewandowska-Bieniek, Joanna; Szczepanek, Joanna; Styczyński, Jan; Tretyn, Andrzej

doi:10.1002/jgm.2889

Cited by 7 publications

(4 citation statements)

References 55 publications

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“…Several studies have shown that the positive expression of ITGAM was closely associated with the prognosis of AML patients [20,21]. A previous study indicated that lncRNA ITGB2 was significantly associated with various immune signatures in AML [22]. Chemokines play an important role in tumor cell migration and infiltration of distant organ sites [23].…”

Section: Discussionmentioning

confidence: 99%

HCK is a Potential Prognostic Biomarker that Correlates with Immune Cell Infiltration in Acute Myeloid Leukemia

Cheng

Wang

et al. 2022

Disease Markers

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Background. The tumor microenvironment (TME) plays a significant role in the progression and prognosis of acute myeloid leukemia (AML). This study is aimed at exploring TME-associated biomarkers and identify their potential mechanism in the microenvironment of AML. Method. In this study, the stromal, immune, and ESTIMATE scores of AML patients were evaluated with the ESTIMATE and CIBERSORT algorithms; then, the AML samples were divided into high- and low-score groups. We evaluated the association between clinicopathological characteristics, survival rate, and the stromal/immune/ESTIMATE scores. Furthermore, we identified TME-associated differentially expressed genes (DEGs) then carried out pathway enrichment analysis, protein-protein interaction (PPI) network, Cox regression analysis, and Kaplan-Meier survival analysis to select the most crucial genes. In addition, we further explored the potential mechanism of HCK in the AML microenvironment. Results. We identified 624 TME-associated DEGs and found that HCK was the most promising biomarker associated with AML. The results of the gene set enrichment analysis (GSEA) indicated that HCK was mainly involved in immune and inflammation-related signaling pathways. In addition, CIBERSORT analysis showed that HCK was closely related to tumor immune infiltration, with HCK expression associated with various infiltrating immune cells, including B cells, T cells, tumor-associated macrophages (TAM), NK cells, plasma cells, eosinophils, and neutrophils. Furthermore, HCK expression was closely related with ELN risk stratification in patients with AML. Conclusion. HCK could regulate immune cell infiltration in the microenvironment of AML and may act as a potential biomarker for the treatment and prognosis of AML patients.

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Section: Discussionmentioning

confidence: 99%

HCK is a Potential Prognostic Biomarker that Correlates with Immune Cell Infiltration in Acute Myeloid Leukemia

Cheng

Wang

et al. 2022

Disease Markers

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“…Applying the collected expression and CGH microarray for analysis, some investigators pointed out that the ITGB2 gene may be one of the reasons why acute leukemia cells antagonize anthracyclines and are not sensitive to relevant chemotherapy regimens. In AML resistance of blasts to idarubicin and mitoxantrone may re ect impaired integrins pathway [29]. The high expression of ITGB2 in triple negative breast cancer affects the prognosis of patients [30].…”

Section: Discussionmentioning

confidence: 99%

ITGB2 Expression is Negatively Correlated with the Prognosis of Acute Myeloid Leukemia

Zhou¹,

Chen²,

Li³

2021

Preprint

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Objective: Acute myeloid leukemia (AML) is a clonal malignant hematological neoplasm with a poor prognosis and high heterogeneity. Many studies have been conducted on the diagnosis and treatment of AML, but the immune microenvironmental mechanisms underlying AML disease progression have not been fully elucidated. The aim of this study was to find the potential genes in tumor microenvironmental mechanisms underlying the initiation and progression of AML through relevant biological informatics analysis, and investigate the potential influence of the gene in tumor microenvironment (TME).Methods: AML samples of genes were retrieved from The Cancer Genome Atlas (TCGA) databases. The number of tumor-infiltrating immune cells (TIC) as well as immune and stromal components in AML cases was calculated using the ESTIMATE and CIBERSORT algorithms. Two methods, COX regression analysis and protein-protein interaction (PPI) network, were applied to obtain related genes, and the intersection of related genes was taken to obtain differentially expressed genes (DEGs). Gene Set Enrichment Analysis (GSEA) was used for explore the biological signaling pathway. CIBERSORT analysis for the proportion of TICs was performed to reveal that TICs which are related of the target gene.Results: Cross-tabulation analysis of univariate COX regression analysis and PPI network known the β2 integrin factor (ITGB2) as a major predictor of AML prognosis. High expression of ITGB2 was correlated with low survival of AML patients. GSEA revealed that the higher the ITGB2 gene expression, the more active the immune-related activity. CIBERSORT analysis of the TICs ratio revealed that 9 kinds of TICs were negatively correlated with the expression of ITGB2, including CD4 memory resting T cells, CD8 T cells, naive B cells, resting NK cells, Plasma cells, follicular helper T cells, resting Mast cells, Eosinophils and activated mast cells. Only monocytes were positively correlated with ITGB2 expression. These results provided further evidence that ITGB2 levels may determine the prognosis of AML patients by modulating the immune status of TME, which provides an additional suggestion for the treatment of AML.

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“…β2 was strongly up-regulated with down-regulated phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) in the AML profile. In AML, the resistance of blasts to idarubicin and mitoxantrone may reflect an impaired integrin pathway (Laskowska et al, 2016). Taken together, β2 is implicated in drug resistance and impaired integrin signalling.…”

Section: Integrin β2 (Itgb2 Cd18)mentioning

confidence: 99%

Targeting integrins in drug‐resistant acute myeloid leukaemia

Ogana

Hurwitz

Wei

et al. 2023

British J Pharmacology

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Acute myeloid leukaemia (AML) continues to have a poor prognosis, warranting new therapeutic strategies. The bone marrow (BM) microenvironment consists of niches that interact with not only normal haematopoietic stem cells (HSC) but also leukaemia cells like AML. There are many adhesion molecules in the BM microenvironment; therein, integrins have been of central interest. AML cells express integrins that bind to ligands in the microenvironment, enabling adhesion of leukaemia cells in the microenvironment, thereby initiating intracellular signalling pathways that are associated with cell migration, cell proliferation, survival, and drug resistance that has been described to mediate cell adhesion‐mediated drug resistance (CAM‐DR). Identifying and targeting integrins in AML to interrupt interactions with the microenvironment have been pursued as a strategy to overcome CAM‐DR. Here, we focus on the BM microenvironment and review the role of integrins in CAM‐DR of AML and discuss integrin‐targeting strategies.

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Genomic and transcriptomic profiles and in vitro resistance to mitoxantrone and idarubicin in pediatric acute leukemias

Abstract: In AML, the resistance of blasts to idarubicin and mitoxantrone may reflect an impaired integrin pathway. In ALL, the development of resistance is caused by the inhibition of B and T cell activation. Copyright © 2016 John Wiley & Sons, Ltd.

Cited by 7 publications

References 55 publications

HCK is a Potential Prognostic Biomarker that Correlates with Immune Cell Infiltration in Acute Myeloid Leukemia

HCK is a Potential Prognostic Biomarker that Correlates with Immune Cell Infiltration in Acute Myeloid Leukemia

ITGB2 Expression is Negatively Correlated with the Prognosis of Acute Myeloid Leukemia

Targeting integrins in drug‐resistant acute myeloid leukaemia

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