Evidence map›Paper›PMID 21921042›Full record

Trial reportBlood2011

Epigenetic and molecular profiles of erythroid cells after hydroxyurea treatment in sickle cell anemia.

Aisha L Walker, Shirley Steward, Thad A Howard, Nicole Mortier, Matthew Smeltzer, Yong-Dong Wang, Russell E Ware

Registry-linked trialOpen access · bronzeAbstract readClinical Trial
In one paragraph

Trial report in Blood, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00305175 (Long Term Effects of Hydroxyurea Therapy in Children With Sickle Cell Disease), which is not on this map. Cited by 43 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed, 2 pooled it
1.4field-weighted citation impact, top 20% 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.

NCT00305175 completednot on this map

Long Term Effects of Hydroxyurea Therapy in Children With Sickle Cell Disease

TypeobservationalSponsorSt. Jude Children's Research HospitalRan2006 to 2015Enrolled260ConditionsSickle Cell Disease
3 · Its place in the literature

Who cites it

43 citing papers in PubMed, 2 syntheses or guidelines pooled it, 63 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. MicroRNA29B induces fetal hemoglobinFrontiers in medicine · 2022
    Article
  14. Article
  15. Exploring epigenetic and microRNA approaches for γ-globin gene regulation.Experimental biology and medicine (Maywood, N.J.) · 2021
    Review
  16. Article
  17. Review
  18. Article
  19. Review
  20. 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 2 institutions in 1 country.

Aisha L WalkerDepartment of Pharmaceutical Sciences, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA. aisha.walker@stjude.org
Shirley Steward
Thad A Howard
Nicole Mortier
Matthew Smeltzer
Yong-Dong Wang
Russell E Ware
Baylor College of Medicine · USSt. Jude Children's Research Hospital · US

Funding

Hydroxyurea Pharmacokinetics and PharmacogenomicsR01HL090941 · NHLBI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI WARE, RUSSELL E · 2008 to 2011
$1.5M
NHLBI NIH HHS R01 HL090941
6 · The paper itself

Abstract

Hydroxyurea has been shown to be efficacious for the treatment of sickle cell anemia (SCA), primarily through the induction of fetal hemoglobin (HbF). However, the exact mechanisms by which hydroxyurea can induce HbF remain incompletely defined, although direct transcriptional effects and altered cell cycle kinetics have been proposed. In this study, we investigated potential epigenetic and alternative molecular mechanisms of hydroxyurea-mediated HbF induction by examining methylation patterns within the (G)γ-globin promoter and miRNA expression within primary CD71(+) erythrocytes of patients with SCA, both at baseline before beginning hydroxyurea therapy and after reaching maximum tolerated dose (MTD). Using both cross-sectional analysis and paired-sample analysis, we found that the highly methylated (G)γ-globin promoter was inversely correlated to baseline HbF levels, but only slightly altered by hydroxyurea treatment. Conversely, expression of several specific miRNAs was significantly increased after hydroxyurea treatment, and expression of miR-26b and miR-151-3p were both associated with HbF levels at MTD. The significant associations identified in these studies suggest that methylation may be important for regulation of baseline HbF, but not after hydroxyurea treatment, whereas changes in miRNA expression may be associated with hydroxyurea-mediated HbF induction. This study was registered at ClinicalTrials.gov (NCT00305175).

Indexed as

AdultAnemia, Sickle CellAntisickling AgentsChildCpG IslandsDNA MethylationEpigenesis, GeneticErythrocytesErythroid CellsFetal HemoglobinGene Expression ProfilingHumansHydroxyureaMicroRNAsProspective StudiesReticulocytesAntisickling AgentsFetal HemoglobinHydroxyureaMicroRNAs

Identifiers

PMID21921042
PMCPMC3217365
OpenAlexW1986055602

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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.