Long non-coding RNA signatures and related signaling pathway in T-cell acute lymphoblastic leukemia

Yousefi, Homayon; Purrahman, Daryush; Jamshidi, Mohammad; Lak, Elena; Keikhaei, Bijan; Mahmoudian-Sani, Mohammad-Reza

doi:10.1007/s12094-022-02886-9

Cited by 10 publications

(3 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Using RNAseq, we tried to identify the differentially expressed noncoding RNAs, especially lncRNAs, which were well documented earlier for their role in cancers. Recent studies have revealed lncRNA's aberrant expression profile in T-ALL, leading to deregulated downstream signaling pathways ( 69 ). An in-depth analysis revealed 2,243 lncRNAs, with 223 showing differential expression.…”

Section: Discussionmentioning

confidence: 99%

Decoding the genetic symphony: Profiling protein-coding and long noncoding RNA expression in T-acute lymphoblastic leukemia for clinical insights

Verma,

Kapoor,

Kumari

et al. 2024

PNAS Nexus

View full text Add to dashboard Cite

T-acute lymphoblastic leukemia (T-ALL) is a heterogeneous malignancy characterized by the abnormal proliferation of immature T-cell precursors. Despite advances in immunophenotypic classification, understanding the molecular landscape and its impact on patient prognosis remains challenging. In this study, we conducted comprehensive RNA sequencing in a cohort of 35 T-ALL patients to unravel the intricate transcriptomic profile. Subsequently, we validated the prognostic relevance of 23 targets, encompassing (i) Protein-coding genes - BAALC, HHEX, MEF2C, FAT1, LYL1, LMO2, LYN, and TAL1; (ii) Epigenetic modifiers - DOT1L, EP300, EML4, RAG1, EZH2, and KDM6A; and (iii) long non-coding RNAs (lncRNAs) - XIST, PCAT18, PCAT14, LINC00202, LINC00461, LINC00648, ST20, MEF2C-AS1, and MALAT1 in an independent cohort of 99 T-ALL patients. Principal component analysis revealed distinct clusters aligning with immunophenotypic subtypes, providing insights into the molecular heterogeneity of T-ALL. The identified signature genes exhibited associations with clinicopathologic features. Survival analysis uncovered several independent predictors of patient outcomes. Higher expression of MEF2C, BAALC, HHEX, and LYL1 genes emerged as robust indicators of poor overall survival (OS), event-free survival (EFS), and relapse-free survival (RFS). Higher LMO2 expression correlated with adverse EFS and RFS outcomes. Intriguingly, increased expression of lncRNA ST20 coupled with RAG1, demonstrated a favorable prognostic impact on OS, EFS, and RFS. Conclusively, several novel associations of gene expression patterns with clinicopathological features and prognosis were identified, which may help understand T-ALL's molecular pathogenesis and provide novel prognostic markers.

show abstract

Section: Discussionmentioning

confidence: 99%

Decoding the genetic symphony: Profiling protein-coding and long noncoding RNA expression in T-acute lymphoblastic leukemia for clinical insights

Verma,

Kapoor,

Kumari

et al. 2024

PNAS Nexus

View full text Add to dashboard Cite

show abstract

“…T-ALL/T-LBL shows high heterogeneity, and despite some advances in the treatment of hematological tumors, patient prognosis remains poor. Current research on T-ALL/T-LBL has focused mainly on identifying the underlying pathways, indicating anti-leukemia therapy's future (77)(78)(79). Targeted therapy for T-ALL/T-LBL could involve multiple aspects, including targeting apoptosis, RTKs, hedgehog-associated signaling, mitochondrial metabolism and respiration, transcriptional control, and immunotherapy (80)(81)(82)(83).…”

Section: Discussionmentioning

confidence: 99%

Key candidate genes and pathways in T lymphoblastic leukemia/lymphoma identified by bioinformatics and serological analyses

Ren,

Liang,

Huang

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

T-cell acute lymphoblastic leukemia (T-ALL)/T-cell lymphoblastic lymphoma (T-LBL) is an uncommon but highly aggressive hematological malignancy. It has high recurrence and mortality rates and is challenging to treat. This study conducted bioinformatics analyses, compared genetic expression profiles of healthy controls with patients having T-ALL/T-LBL, and verified the results through serological indicators. Data were acquired from the GSE48558 dataset from Gene Expression Omnibus (GEO). T-ALL patients and normal T cells-related differentially expressed genes (DEGs) were investigated using the online analysis tool GEO2R in GEO, identifying 78 upregulated and 130 downregulated genes. Gene Ontology (GO) and protein-protein interaction (PPI) network analyses of the top 10 DEGs showed enrichment in pathways linked to abnormal mitotic cell cycles, chromosomal instability, dysfunction of inflammatory mediators, and functional defects in T-cells, natural killer (NK) cells, and immune checkpoints. The DEGs were then validated by examining blood indices in samples obtained from patients, comparing the T-ALL/T-LBL group with the control group. Significant differences were observed in the levels of various blood components between T-ALL and T-LBL patients. These components include neutrophils, lymphocyte percentage, hemoglobin (HGB), total protein, globulin, erythropoietin (EPO) levels, thrombin time (TT), D-dimer (DD), and C-reactive protein (CRP). Additionally, there were significant differences in peripheral blood leukocyte count, absolute lymphocyte count, creatinine, cholesterol, low-density lipoprotein, folate, and thrombin times. The genes and pathways associated with T-LBL/T-ALL were identified, and peripheral blood HGB, EPO, TT, DD, and CRP were key molecular markers. This will assist the diagnosis of T-ALL/T-LBL, with applications for differential diagnosis, treatment, and prognosis.

show abstract

“…Through comprehensive RNA-Seq profiling, an accumulated number of studies have indicated that lncRNAs play critical roles in T-ALL pathogenesis [ 89 , 90 , 91 , 92 ]. In this regard, Yang et al reported that SNHG1 is upregulated in T-ALL under in vivo and in vitro conditions and has a tumor suppressor effect through interactions with miR 124-3P.…”

Section: Alterations In Lncrnas In Lymphoid Malignancymentioning

confidence: 99%

Long Non-Coding RNA Signatures in Lymphopoiesis and Lymphoid Malignancies

Baghdadi

Heidari

Zavvar

et al. 2023

ncRNA

View full text Add to dashboard Cite

Lymphoid cells play a critical role in the immune system, which includes three subgroups of T, B, and NK cells. Recognition of the complexity of the human genetics transcriptome in lymphopoiesis has revolutionized our understanding of the regulatory potential of RNA in normal lymphopoiesis and lymphoid malignancies. Long non-coding RNAs (lncRNAs) are a class of RNA molecules greater than 200 nucleotides in length. LncRNAs have recently attracted much attention due to their critical roles in various biological processes, including gene regulation, chromatin organization, and cell cycle control. LncRNAs can also be used for cell differentiation and cell fate, as their expression patterns are often specific to particular cell types or developmental stages. Additionally, lncRNAs have been implicated in lymphoid differentiation, such as regulating T-cell and B-cell development, and their expression has been linked to immune-associated diseases such as leukemia and lymphoma. In addition, lncRNAs have been investigated as potential biomarkers for diagnosis, prognosis, and therapeutic response to disease management. In this review, we provide an overview of the current knowledge about the regulatory role of lncRNAs in physiopathology processes during normal lymphopoiesis and lymphoid leukemia.

show abstract

Long non-coding RNA signatures and related signaling pathway in T-cell acute lymphoblastic leukemia

Cited by 10 publications

References 63 publications

Decoding the genetic symphony: Profiling protein-coding and long noncoding RNA expression in T-acute lymphoblastic leukemia for clinical insights

Decoding the genetic symphony: Profiling protein-coding and long noncoding RNA expression in T-acute lymphoblastic leukemia for clinical insights

Key candidate genes and pathways in T lymphoblastic leukemia/lymphoma identified by bioinformatics and serological analyses

Long Non-Coding RNA Signatures in Lymphopoiesis and Lymphoid Malignancies

Contact Info

Product

Resources

About