Evidence map›Paper›PMID 24795534›Full record

ArticleCancer cell international2014

Epigenetic alteration by DNA-demethylating treatment restores apoptotic response to glucocorticoids in dexamethasone-resistant human malignant lymphoid cells.

Aaron L Miller, Chuandong Geng, Georgiy Golovko, Meenakshi Sharma, Jason R Schwartz, Jiabin Yan, Lawrence Sowers, William R Widger, Yuriy Fofanov, Wayne V Vedeckis and 1 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer cell international, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.5field-weighted citation impact, top 34% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 11 citations in OpenAlex.

  1. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 4 institutions in 1 country.

Aaron L MillerDepartment of Biochemistry & Molecular Biology, (ALM present address, Department. of Pediatrics, & Assay Devel. Service Division Galveston National Lab.), University of Texas Medical Branch, Galveston, TX, USA.
Chuandong GengDepartment of Biochemistry & Molecular Biology, Louisiana State University Health Sciences Center, New Orleans, LA CG present address, Depts. of Medicine and of Molecular & Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
Georgiy GolovkoDepartment of Biology & Biochemistry, Centers for Biomedical & Environmental Genomics and/or Nuclear Receptors & Cell Signaling, University of Houston, Houston, TX, USA ; Department of Pharmacology & Toxicology, and Sealy Center for Structural Biology & Molecular Biophysics, Univ. of Texas Medical Branch, Galveston, TX, USA.
Meenakshi SharmaDepartment of Biology & Biochemistry, Centers for Biomedical & Environmental Genomics and/or Nuclear Receptors & Cell Signaling, University of Houston, Houston, TX, USA.
Jason R SchwartzDepartment of Biochemistry & Molecular Biology, Louisiana State University Health Sciences Center, New Orleans, LA CG present address, Depts. of Medicine and of Molecular & Cellular Biology, Baylor College of Medicine, Houston, TX, USA ; Present address St. Jude Children's Hospital, Memphis, TN, USA.
Jiabin YanDepartment of Pharmacology & Toxicology, and Sealy Center for Structural Biology & Molecular Biophysics, Univ. of Texas Medical Branch, Galveston, TX, USA.
Lawrence SowersDepartment of Pharmacology & Toxicology, and Sealy Center for Structural Biology & Molecular Biophysics, Univ. of Texas Medical Branch, Galveston, TX, USA.
William R WidgerDepartment of Biology & Biochemistry, Centers for Biomedical & Environmental Genomics and/or Nuclear Receptors & Cell Signaling, University of Houston, Houston, TX, USA.
Yuriy FofanovDepartment of Biology & Biochemistry, Centers for Biomedical & Environmental Genomics and/or Nuclear Receptors & Cell Signaling, University of Houston, Houston, TX, USA ; Department of Pharmacology & Toxicology, and Sealy Center for Structural Biology & Molecular Biophysics, Univ. of Texas Medical Branch, Galveston, TX, USA.
Wayne V VedeckisDepartment of Biochemistry & Molecular Biology, Louisiana State University Health Sciences Center, New Orleans, LA CG present address, Depts. of Medicine and of Molecular & Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
E Brad ThompsonDepartment of Biochemistry & Molecular Biology, (ALM present address, Department. of Pediatrics, & Assay Devel. Service Division Galveston National Lab.), University of Texas Medical Branch, Galveston, TX, USA ; Department of Biology & Biochemistry, Centers for Biomedical & Environmental Genomics and/or Nuclear Receptors & Cell Signaling, University of Houston, Houston, TX, USA.
University of Houston · USThe University of Texas Medical Branch at Galveston · USLouisiana State University Health Sciences Center New Orleans · USBaylor College of Medicine · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundGlucocorticoids (GCs) are often included in the therapy of lymphoid malignancies because they kill several types of malignant lymphoid cells. GCs activate the glucocorticoid receptor (GR), to regulate a complex genetic network, culminating in apoptosis. Normal lymphoblasts and many lymphoid malignancies are sensitive to GC-driven apoptosis. Resistance to GCs can be a significant clinical problem, however, and correlates with resistance to several other major chemotherapeutic agents.

methodsWe analyzed the effect of treatment with the cytosine analogue 5 aza-2' deoxycytidine (AZA) on GC resistance in two acute lymphoblastic leukemia (T or pre-T ALL) cell lines- CEM and Molt-4- and a (B-cell) myeloma cell line, RPMI 8226. Methods employed included tissue culture, flow cytometry, and assays for clonogenicity, cytosine extension, immunochemical identification of proteins, and gene transactivation. High throughput DNA sequencing was used to confirm DNA methylation status.

conclusionsTreatment of these cells with AZA resulted in altered DNA methylation and restored GC-evoked apoptosis in all 3 cell lines. In CEM cells the altered epigenetic state resulted in site-specific phosphorylation of the GR, increased GR potency, and GC-driven induction of the GR from promoters that lie in CpG islands. In RPMI 8226 cells, expression of relevant coregulators of GR function was altered. Activation of p38 mitogen-activated protein kinase (MAPK), which is central to a feed-forward mechanism of site-specific GR phosphorylation and ultimately, apoptosis, occurred in all 3 cell lines. These data show that in certain malignant hematologic B- and T-cell types, epigenetically controlled GC resistance can be reversed by cell exposure to a compound that causes DNA demethylation. The results encourage studies of application to in vivo systems, looking towards eventual clinical applications.

Indexed as

5 Aza-2’ deoxycytidineApoptosisCEMDexamethasoneEpigeneticGlucocorticoidGlucocorticoid receptorHigh throughput sequencingLeukemiaLymphoidMethylationMolt-4Myelomap38PhosphorylationRPMI 8226

Identifiers

PMID24795534
PMCPMC4008436
OpenAlexW2097151124

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.