RNA sequencing analyses reveal differentially expressed genes and pathways as Notch2 targets in B-cell lymphoma

Arasu, Ashok; Balakrishnan, Pavithra; Velusamy, Thirunavukkarasu

doi:10.18632/oncotarget.27805

Cited by 3 publications

(2 citation statements)

References 51 publications

(60 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, recent studies have demonstrated that Notch2 is able to regulate other fundamental cellular pathways such as PI3K/AKT and NF-kB. Notch2 oncogenic effects could be mediated by these downstream pathways, but further analyzes are necessary to evaluate this possible cross-talk ( 117 ). On the other hand, the therapeutic inhibition of Bruton tyrosine kinase (BTK), a crucial component of B cell receptor signaling, is not influenced by Notch2 mutational status ( 118 ).…”

Section: Notch2 In Splenic and Nodal Marginal Zone Lymphomamentioning

confidence: 99%

Role of Notch2 pathway in mature B cell malignancies

Mesini

Fiorcari²,

Atene³

et al. 2023

Front. Oncol.

View full text Add to dashboard Cite

In recent decades, the Notch pathway has been characterized as a key regulatory signaling of cell-fate decisions evolutionarily conserved in many organisms and different tissues during lifespan. At the same time, many studies suggest a link between alterations of this signaling and tumor genesis or progression. In lymphopoiesis, the Notch pathway plays a fundamental role in the correct differentiation of T and B cells, but its deregulated activity leads to leukemic onset and evolution. Notch and its ligands Delta/Jagged exhibit a pivotal role in the crosstalk between leukemic cells and their environment. This review is focused in particular on Notch2 receptor activity. Members of Notch2 pathway have been reported to be mutated in Chronic Lymphocytic Leukemia (CLL), Splenic Marginal Zone Lymphoma (SMZL) and Nodal Marginal Zone Lymphoma (NMZL). CLL is a B cell malignancy in which leukemic clones establish supportive crosstalk with non-malignant cells of the tumor microenvironment to grow, survive, and resist even the new generation of drugs. SMZL and NMZL are indolent B cell neoplasms distinguished by a distinct pattern of dissemination. In SMZL leukemic cells affect mainly the spleen, bone marrow, and peripheral blood, while NMZL has a leading nodal distribution. Since Notch2 is involved in the commitment of leukemic cells to the marginal zone as a major regulator of B cell physiological differentiation, it is predominantly affected by the molecular lesions found in both SMZL and NMZL. In light of these findings, a better understanding of the Notch receptor family pathogenic role, in particular Notch2, is desirable because it is still incomplete, not only in the physiological development of B lymphocytes but also in leukemia progression and resistance. Several therapeutic strategies capable of interfering with Notch signaling, such as monoclonal antibodies, enzyme or complex inhibitors, are being analyzed. To avoid the unwanted multiple “on target” toxicity encountered during the systemic inhibition of Notch signaling, the study of an appropriate pharmaceutical formulation is a pressing need. This is why, to date, there are still no Notch-targeted therapies approved. An accurate analysis of the Notch pathway could be useful to drive the discovery of new therapeutic targets and the development of more effective therapies.

show abstract

Section: Notch2 In Splenic and Nodal Marginal Zone Lymphomamentioning

confidence: 99%

Role of Notch2 pathway in mature B cell malignancies

Mesini

Fiorcari²,

Atene³

et al. 2023

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…By using microarray gene expression, thousands of genes can be surveyed at the same time, and the analysis of tumor tissues may contribute to understanding the biological mechanisms underlying lymphoblast transformation and ALL progression. Additionally, microarray analysis may allow us to identify potential biomarkers with clinical significance, new therapeutic targets, and genes involved in drug resistance and relapse [18][19][20]. In this study, we performed the first transcriptomic analysis in Mexican adults with ALL to identify abnormally expressed genes.…”

Section: Introductionmentioning

confidence: 99%

Transcriptome Analysis in Mexican Adults with Acute Lymphoblastic Leukemia

Cruz-Miranda,

Olarte-Carrillo,

Bárcenas-López

et al. 2024

IJMS

View full text Add to dashboard Cite

Acute lymphoblastic leukemia (ALL) represents around 25% of adult acute leukemias. Despite the increasing improvement in the survival rate of ALL patients during the last decade, the heterogeneous clinical and molecular features of this malignancy still represent a major challenge for treatment and achieving better outcomes. To identify aberrantly expressed genes in bone marrow (BM) samples from adults with ALL, transcriptomic analysis was performed using Affymetrix Human Transcriptome Array 2.0 (HTA 2.0). Differentially expressed genes (DEGs) (±2-fold change, p-value < 0.05, and FDR < 0.05) were detected using the Transcriptome Analysis Console. Gene Ontology (GO), Database for Annotation, Visualization, and Integrated Discovery (DAVID), and Ingenuity Pathway Analysis (IPA) were employed to identify gene function and define the enriched pathways of DEGs. The protein–protein interactions (PPIs) of DEGs were constructed. A total of 871 genes were differentially expressed, and DNTT, MYB, EBF1, SOX4, and ERG were the top five up-regulated genes. Meanwhile, the top five down-regulated genes were PTGS2, PPBP, ADGRE3, LUCAT1, and VCAN. An association between ERG, CDK6, and SOX4 expression levels and the probability of relapse and death was observed. Regulation of the immune system, immune response, cellular response to stimulus, as well as apoptosis signaling, inflammation mediated by chemokines and cytokines, and T cell activation were among the most altered biological processes and pathways, respectively. Transcriptome analysis of ALL in adults reveals a group of genes consistently associated with hematological malignancies and underscores their relevance in the development of ALL in adults.

show abstract

NOTCH signaling in the pathogenesis of splenic marginal zone lymphoma—opportunities for therapy

Alderuccio

2021

Leukemia & Lymphoma

View full text Add to dashboard Cite

RNA sequencing analyses reveal differentially expressed genes and pathways as Notch2 targets in B-cell lymphoma

Cited by 3 publications

References 51 publications

Role of Notch2 pathway in mature B cell malignancies

Role of Notch2 pathway in mature B cell malignancies

Transcriptome Analysis in Mexican Adults with Acute Lymphoblastic Leukemia

NOTCH signaling in the pathogenesis of splenic marginal zone lymphoma—opportunities for therapy

Contact Info

Product

Resources

About