Evidence map›Paper›PMID 38134183›Full record

ArticlePloS one2023

Effect of the LSD1 inhibitor RN-1 on γ-globin and global gene expression during erythroid differentiation in baboons (Papio anubis).

Vinzon Ibanez, Kestis Vaitkus, Maria Armila Ruiz, Zhengdeng Lei, Mark Maienschein-Cline, Zarema Arbieva, Donald Lavelle

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.3field-weighted citation impact, top 30% 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

3 citing papers in PubMed, 1 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
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

7 authors at 1 institution in 1 country.

Vinzon IbanezDepartment of Medicine, University of Illinois at Chicago, Chicago, Illinois, United States of America.
Kestis VaitkusDepartment of Medicine, University of Illinois at Chicago, Chicago, Illinois, United States of America.
Maria Armila RuizDepartment of Medicine, University of Illinois at Chicago, Chicago, Illinois, United States of America.
Zhengdeng LeiResearch Informatics Core, University of Illinois at Chicago, Chicago, Illinois, United States of America.
Mark Maienschein-ClineResearch Informatics Core, University of Illinois at Chicago, Chicago, Illinois, United States of America.
Zarema ArbievaGenomics Research Core, University of Illinois at Chicago, Chicago, Illinois, United States of America.
Donald LavelleDepartment of Medicine, University of Illinois at Chicago, Chicago, Illinois, United States of America.ORCID 0000-0002-0275-7168
University of Illinois Chicago · US

Funding

Strengthening Stakeholder Engagement in Human Research Protections.UL1TR002003 · NCATS · UNIVERSITY OF ILLINOIS AT CHICAGO · PI KARNIK, NIRANJAN SUBHASH, MERMELSTEIN, ROBIN J. · 2016 to 2024
$33.7M
Targeting Enzymatic Regulation of Fetal Hemoglobin RepressionP01HL146372 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SAUNTHARARAJAH, YOGEN · 2019 to 2023
$10.9M
NCATS NIH HHS UL1 TR002003NHLBI NIH HHS P01 HL146372
6 · The paper itself

Abstract

Elevated levels of Fetal Hemoglobin interfere with polymerization of sickle hemoglobin thereby reducing anemia, lessening the severity of symptoms, and increasing life span of patients with sickle cell disease. An affordable, small molecule drug that stimulates HbF expression in vivo would be ideally suited to treat the large numbers of SCD patients that exist worldwide. Our previous work showed that administration of the LSD1 (KDM1A) inhibitor RN-1 to normal baboons increased Fetal Hemoglobin (HbF) and was tolerated over a prolonged treatment period. HbF elevations were associated with changes in epigenetic modifications that included increased levels of H3K4 di-and tri-methyl lysine at the γ-globin promoter. While dramatic effects of the loss of LSD1 on hematopoietic differentiation have been observed in murine LSD1 gene deletion and silencing models, the effect of pharmacological inhibition of LSD1 in vivo on hematopoietic differentiation is unknown. The goal of these experiments was to investigate the in vivo mechanism of action of the LSD1 inhibitor RN-1 by determining its effect on γ-globin expression in highly purified subpopulations of bone marrow erythroid cells enriched for varying stages of erythroid differentiation isolated directly from baboons treated with RN-1 and also by investigating the effect of RN1 on the global transcriptome in a highly purified population of proerythroblasts. Our results show that RN-1 administered to baboons targets an early event during erythroid differentiation responsible for γ-globin repression and increases the expression of a limited number of genes including genes involved in erythroid differentiation such as GATA2, GFi-1B, and LYN.

Indexed as

Anemia, Sickle CellHistone DemethylasesAnimalsFetal Hemoglobingamma-GlobinsGene ExpressionHumansMicePapio anubisFetal Hemoglobingamma-GlobinsHistone DemethylasesKDM1A protein, human

Identifiers

PMID38134183
PMCPMC10745162
OpenAlexW4390100310

What Socratic holds

Textmetadata
LicenceCC0
Read underepoch 390

Registered trials

None linked

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 Socratic graph.