scholarly journals Predicting interactome network perturbations in human cancer: application to gene fusions in acute lymphoblastic leukemia

2014 ◽  
Vol 25 (24) ◽  
pp. 3973-3985 ◽  
Author(s):  
Leon Juvenal Hajingabo ◽  
Sarah Daakour ◽  
Maud Martin ◽  
Reinhard Grausenburger ◽  
Renate Panzer-Grümayer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Lymphoblastic Leukemia ◽  
Human Cancer ◽  
Lymphoblastic Leukemia ◽  
Point Mutations ◽  
Genetic Alterations ◽  
Gene Fusions ◽  
Novel Approach ◽  
Interactome Network ◽  
Cell Acute Lymphoblastic Leukemia

Genomic variations such as point mutations and gene fusions are directly or indirectly associated with human diseases. They are recognized as diagnostic, prognostic markers and therapeutic targets. However, predicting the functional effect of these genetic alterations beyond affected genes and their products is challenging because diseased phenotypes are likely dependent of complex molecular interaction networks. Using as models three different chromosomal translocations—ETV6-RUNX1 (TEL-AML1), BCR-ABL1, and TCF3-PBX1 (E2A-PBX1)—frequently found in precursor-B-cell acute lymphoblastic leukemia (preB-ALL), we develop an approach to extract perturbed molecular interactions from gene expression changes. We show that the MYC and JunD transcriptional circuits are specifically deregulated after ETV6-RUNX1 and TCF3-PBX1 gene fusions, respectively. We also identified the bulk mRNA NXF1-dependent machinery as a direct target for the TCF3-PBX1 fusion protein. Through a novel approach combining gene expression and interactome data analysis, we provide new insight into TCF3-PBX1 and ETV6-RUNX1 acute lymphoblastic leukemia.

Glyoxyl analogs of indole phytoalexins: Synthesis and anticancer activity

2010 ◽  
Vol 75 (8) ◽  
pp. 887-903 ◽  
Author(s):  
Peter Kutschy ◽  
Andrej Sýkora ◽  
Zuzana Čurillová ◽  
Mária Repovská ◽  
Martina Pilátová ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Cell Line ◽  
Human Cancer ◽  
Lymphoblastic Leukemia ◽  
Breast Adenocarcinoma ◽  
Human Cancer Cell Lines ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Indole Phytoalexins

Glyoxyl analogs of indole phytoalexins brassinin, 1-methoxybrassinin, brassitin, 1-methoxybrassitin and 1-methoxybrassenin B were prepared, using (1H-indol-3-yl)-, (1-methoxyindol-3-yl)- and [1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)indol-3-yl]glyoxyl chlorides as starting compounds. Synthesized products were examined for their antiproliferative activity against human cancer cell lines Jurkat (T-cell acute lymphoblastic leukemia), MCF-7 (breast adenocarcinoma, estrogen receptor-positive), MDA-MB-231 (breast adenocarcinoma, estrogen receptor-negative), HeLa (cervical adenocarcinoma), CCRF-CEM cell line (T-cell acute lymphoblastic leukemia) and A-549 cell line (lung adenocarcinoma), and their activity compared with natural phytoalexins and corresponding (1H-indol-3-yl)acetic acid derivatives. The highest potency with IC50 3.3–66.1 μmol l–1 was found for glyoxyl analogs of 1-methoxybrassenin B.

Abstract 478: Predicting interactome networks perturbations in human cancer: application to gene fusions in acute lymphoblastic leukemia

2014 ◽  
Author(s):  
Leon Hajingabo ◽  
Sarah Daakour ◽  
Maud Martin ◽  
Reinhard Grausenburger ◽  
Renate Panzer-Grümayer ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Human Cancer ◽  
Lymphoblastic Leukemia ◽  
Gene Fusions

scholarly journals Clinical characterization and prognosis of T cell acute lymphoblastic leukemia with high CRLF2 gene expression in children

PLoS ONE ◽  
2019 ◽  
Vol 14 (12) ◽  
pp. e0224652
Author(s):  
Mingmin Wang ◽  
Jinquan Wen ◽  
Yuxia Guo ◽  
Yali Shen ◽  
Xizhou An ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Lymphoblastic Leukemia ◽  
Cell Acute Lymphoblastic Leukemia

Transcriptome Analysis (Rnaseq) Detects Gene Fusions and Point Mutations Associated with Ph-Like Acute Lymphoblastic Leukemia

2015 ◽  
Vol 208 (6) ◽  
pp. 358
Author(s):  
Kai Lee Yap ◽  
Chaitanya Bandlamudi ◽  
Christopher Mariani ◽  
Larissa Furtado ◽  
Gordana Raca
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Transcriptome Analysis ◽  
Lymphoblastic Leukemia ◽  
Point Mutations ◽  
Gene Fusions

Down-Regulation of Mir-26b and Its Inhibition on the Growth of T Cell Acute Lymphoblastic Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2440-2440
Author(s):  
Tian Yuan ◽  
Yaling Yang ◽  
Jeffrey You ◽  
Daniel Lin ◽  
Kefeng Lin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Cell Growth ◽  
Cell Lines ◽  
Lymphoblastic Leukemia ◽  
Expression Level ◽  
Rt Pcr ◽  
Altered Expression ◽  
Cell Acute Lymphoblastic Leukemia

Abstract Introduction: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy accounting for 15% of pediatric and 25% of adult acute lymphoblastic leukemia (ALL) cases. With current chemotherapies and transplantation therapy, there are still 25-50% T-ALL patients that suffer from relapse and have a poor outcome. MicroRNAs (miRNAs or miRs) are endogenous small non-coding RNAs (containing about 22 nucleotides in length). miRs function at posttranscriptional level as negative regulators of gene expression and exert their regulatory function through binding to target mRNAs and silencing gene expression. To better understand the pathogenesis and develop the new therapeutic targets of T-ALL, we have developed a Pten tumor suppressor knockout T-ALL mouse model and profiled miRs from the mouse Pten deficient T-ALL. miR-26b was one of the miRs that were found down-regulated in the mouse Pten deficient T-ALL. Recent studies showed that the aberrant expression of miR-26b is implicated in several types of cancer. The expression level of miR-26b and its role of in T-ALL, however, are unknown. We investigated if the expression level of miR-26b is aberrant in T-ALL and the effect of potentially altered expression on the growth of human T-ALL cells. Methods: We conducted miR array profiling to identify differentially expressed miRs in the mouse Pten deficient T-ALLs compared with preneoplastic thymocyte controls. We validated expression levels of several miRs, including miR-26b, that are differentially expressed in mouse and human T-ALL cells using quantitative RT-PCR. We also overexpressed miR-26b using a lentivirus based vector in human T-ALL cell lines to assess its effect on cell growth and apoptosis. Results: Employing miR array profiling, we identified a subset of miRs that exhibited marked altered expression in the mouse Pten deficient T-ALL cells. Quantitative RT-PCR validated that the expression level of miR-26b in the mouse Pten deficient T-ALL cells was markedly lower in comparison to that of preneoplastic thymocytes. To determine if miR-26b expression level is also altered in human T-ALL, we performed quantitative RT-PCR on a panel of human T-ALL cell lines. Indeed, the expression level of miR-26b is significantly lower in the human T-ALL cell lines when compared with that of normal thymocytes. To functionally assess if miR-26b plays a role in the cell growth of human T-ALL cells, we expressed exogenous miR-26b in a panel of human T-ALL cell lines. We demonstrated that the expression of exogenous miR-26b significantly reduced the proliferation and promoted apoptosis of several human T-ALL cell lines. Conclusions: Our results demonstrated that miR-26b is down-regulated in T-ALL and the expression of exogenous miR-26b elicits deceased cell proliferation and increased apoptosis of human T-ALL. These results suggest that miR-26b may function as a tumor suppressor in the development of T-ALL and further characterization of the target and regulation of miR-26b may have therapeutic implications. Disclosures No relevant conflicts of interest to declare.

scholarly journals Integrated genomic analysis of relapsed childhood acute lymphoblastic leukemia reveals therapeutic strategies

Blood ◽  
2011 ◽  
Vol 118 (19) ◽  
pp. 5218-5226 ◽  
Author(s):  
Laura E. Hogan ◽  
Julia A. Meyer ◽  
Jun Yang ◽  
Jinhua Wang ◽  
Nicholas Wong ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Genomic Analysis ◽  
Genetic Alterations ◽  
Mitogen Activated Protein Kinase ◽  
Genetic Changes ◽  
Mitogen Activated Protein ◽  
Dna Methylation Analysis

Abstract Despite an increase in survival for children with acute lymphoblastic leukemia (ALL), the outcome after relapse is poor. To understand the genetic events that contribute to relapse and chemoresistance and identify novel targets of therapy, 3 high-throughput assays were used to identify genetic and epigenetic changes at relapse. Using matched diagnosis/relapse bone marrow samples from children with relapsed B-precursor ALL, we evaluated gene expression, copy number abnormalities (CNAs), and DNA methylation. Gene expression analysis revealed a signature of differentially expressed genes from diagnosis to relapse that is different for early (< 36 months) and late (≥ 36 months) relapse. CNA analysis discovered CNAs that were shared at diagnosis and relapse and others that were new lesions acquired at relapse. DNA methylation analysis found increased promoter methylation at relapse. There were many genetic alterations that evolved from diagnosis to relapse, and in some cases these genes had previously been associated with chemoresistance. Integration of the results from all 3 platforms identified genes of potential interest, including CDKN2A, COL6A2, PTPRO, and CSMD1. Although our results indicate that a diversity of genetic changes are seen at relapse, integration of gene expression, CNA, and methylation data suggest a possible convergence on the WNT and mitogen-activated protein kinase pathways.

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