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Combinatorial epigenetic therapy in diffuse large B cell lymphoma pre-clinical models and patients

Overview of attention for article published in Clinical Epigenetics, July 2016
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Title
Combinatorial epigenetic therapy in diffuse large B cell lymphoma pre-clinical models and patients
Published in
Clinical Epigenetics, July 2016
DOI 10.1186/s13148-016-0245-y
Pubmed ID
Authors

Benet Pera, Tiffany Tang, Rossella Marullo, Shao-Ning Yang, Haelee Ahn, Jayeshkumar Patel, Rebecca Elstrom, Jia Ruan, Richard Furman, John Leonard, Leandro Cerchietti, Peter Martin

Abstract

Refractory and/or relapsed diffuse large B cell lymphoma (RR-DLBCL) patients are incurable with conventional chemotherapy due to the aggressiveness and the chemorefractory state of these tumors. DNA hypermethylation and histone deacetylation are two major epigenetic modifications by which aggressive DLBCL maintain their oncogenic state. We have previously reported that DNA methyltransferase inhibitors (DNMTI) affect RR-DLBCL growth and improve chemosensitivity. Here, we hypothesized that the combination of DNMTI with histone deacetylase inhibitor (HDI) would be an active and feasible therapeutic strategy in RR-DLBCL. Thus, we evaluated the anti-lymphoma activity of the HDI vorinostat (VST) in combination with the DNMTI azacitidine (AZA) or decitabine (DAC) in pre-clinical models of RR-DLBCL, and we determined the feasibility of the combination by conducting a phase Ib trial in RR-DLBCL patients. Concurrent combination of DNMTI and HDI resulted in synergistic anti-lymphoma effect toward RR-DLBCL cells in vitro and in vivo, with no significant toxicity increase. In a phase Ib trial, a total of 18 patients with a median of three prior therapies were treated with four different dose levels of AZA and VST. The most common toxicities were hematological, followed by gastrointestinal and metabolic. The clinical benefit was low as only one subject had a partial response and three subjects had stable disease. Interestingly, two of the seven patients that received additional chemotherapy post-study achieved a complete response and three others had a significant clinical benefit. These observations suggested that the combination might have a delayed chemosensitization effect that we were able to confirm by using in vitro and in vivo models. These studies also demonstrated that the addition of VST does not improve the chemosensitizing effect of DAC alone. Our data supports the strategy of epigenetic priming by employing DNMTI in RR-DLBCL patients in order to overcome resistance and improve their outcomes.

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The data shown below were collected from the profiles of 9 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 54 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 54 100%

Demographic breakdown

Readers by professional status Count As %
Other 7 13%
Student > Master 7 13%
Student > Bachelor 6 11%
Researcher 6 11%
Professor > Associate Professor 4 7%
Other 9 17%
Unknown 15 28%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 13 24%
Medicine and Dentistry 13 24%
Pharmacology, Toxicology and Pharmaceutical Science 3 6%
Agricultural and Biological Sciences 3 6%
Computer Science 1 2%
Other 3 6%
Unknown 18 33%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 5. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 29 July 2016.
All research outputs
#5,905,733
of 22,881,154 outputs
Outputs from Clinical Epigenetics
#367
of 1,259 outputs
Outputs of similar age
#100,473
of 364,027 outputs
Outputs of similar age from Clinical Epigenetics
#11
of 21 outputs
Altmetric has tracked 22,881,154 research outputs across all sources so far. This one has received more attention than most of these and is in the 73rd percentile.
So far Altmetric has tracked 1,259 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.5. This one has gotten more attention than average, scoring higher than 70% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 364,027 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 71% of its contemporaries.
We're also able to compare this research output to 21 others from the same source and published within six weeks on either side of this one. This one is in the 47th percentile – i.e., 47% of its contemporaries scored the same or lower than it.