Evidence map›Paper›PMID 25469886›Full record

ArticlePloS one2014

Lenalidomide induces lipid raft assembly to enhance erythropoietin receptor signaling in myelodysplastic syndrome progenitors.

Kathy L McGraw, Ashley A Basiorka, Joseph O Johnson, Justine Clark, Gisela Caceres, Eric Padron, Ruth Heaton, Yukiyasu Ozawa, Sheng Wei, Lubomir Sokol and 1 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.3field-weighted citation impact, top 21% 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

14 citing papers in PubMed, 33 citations in OpenAlex.

  1. Trial
  2. Lenalidomide-Epoetin Alfa Versus Lenalidomide Monotherapy in Myelodysplastic Syndromes Refractory to Recombinant Erythropoietin.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2021
    Trial
  3. Trial
  4. Review
  5. Article
  6. Review
  7. Review
  8. Review
  9. Therapy for lower-risk MDS.Hematology. American Society of Hematology. Education Program · 2020
    Article
  10. Clinical update on hypomethylating agents.International journal of hematology · 2019
    Review
  11. Review
  12. Article
  13. Where Does Lenalidomide Fit in Non-del(5q) MDS?Current hematologic malignancy reports · 2015
    Review
  14. Article
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 3 institutions in 2 countries.

Kathy L McGrawDepartment of Malignant Hematology, H. Lee Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612, United States of America.
Ashley A BasiorkaDepartment of Malignant Hematology, H. Lee Moffitt Cancer Center-Cancer Biology Ph.D. Program, University of South Florida, 12902 Magnolia Drive, Tampa, FL, 33612, United States of America.
Joseph O JohnsonAnalytic Microscopy Core Facility, H. Lee Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL, 33612, United States of America.
Justine ClarkDepartment of Malignant Hematology, H. Lee Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612, United States of America.
Gisela CaceresMorsani Molecular Diagnostic Laboratory, H. Lee Moffitt Cancer Center, 10902 N. McKinley Drive, Tampa, FL, 33612, United States of America.
Eric PadronDepartment of Malignant Hematology, H. Lee Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612, United States of America.
Ruth HeatonDepartment of Pathology, University of Arizona, 1501 N Campbell Ave, Tucson, AZ, 85724, United States of America.
Yukiyasu OzawaDepartment of Hematology, Japanese Red Cross Nagoya First Hospital, 3-35 Michishita-cho, Nakamura-ku, Aichi, 453-8511, Japan.
Sheng WeiDepartment of Immunology, H. Lee Moffitt Cancer Center, 12902 Magnolia Drive Tampa, FL, 33612, United States of America.
Lubomir SokolDepartment of Malignant Hematology, H. Lee Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612, United States of America.
Alan F ListDepartment of Malignant Hematology, H. Lee Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612, United States of America.
Moffitt Cancer Center · USJapanese Red Cross Nagoya Daiichi Hospital · JPUniversity of Arizona · US

Funding

TRANSLATIONAL RESEARCHP30CA076292 · NCI · UNIVERSITY OF SOUTH FLORIDA · PI KENNETH Lynn WRIGHT · 1998 to 2026
$93.5M
Tumor Immunology Training Program -1 T32 CA115308-A1T32CA115308 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI WRIGHT, KENNETH LYNN · 2007 to 2017
$2.8M
Phosphatase Targets of Lenalidomide in Myelodysplastic SyndromeR01CA131076 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI LIST, ALAN F · 2008 to 2012
$2.2M
NCI NIH HHS P30 CA076292NCI NIH HHS R01 CA131076NCI NIH HHS T32 CA115308
6 · The paper itself

Abstract

Anemia remains the principal management challenge for patients with lower risk Myelodysplastic Syndromes (MDS). Despite appropriate cytokine production and cellular receptor display, erythropoietin receptor (EpoR) signaling is impaired. We reported that EpoR signaling is dependent upon receptor localization within lipid raft microdomains, and that disruption of raft integrity abolishes signaling capacity. Here, we show that MDS erythroid progenitors display markedly diminished raft assembly and smaller raft aggregates compared to normal controls (p = 0.005, raft number; p = 0.023, raft size). Because lenalidomide triggers raft coalescence in T-lymphocytes promoting immune synapse formation, we assessed effects of lenalidomide on raft assembly in MDS erythroid precursors and UT7 cells. Lenalidomide treatment rapidly induced lipid raft formation accompanied by EpoR recruitment into raft fractions together with STAT5, JAK2, and Lyn kinase. The JAK2 phosphatase, CD45, a key negative regulator of EpoR signaling, was displaced from raft fractions. Lenalidomide treatment prior to Epo stimulation enhanced both JAK2 and STAT5 phosphorylation in UT7 and primary MDS erythroid progenitors, accompanied by increased STAT5 DNA binding in UT7 cells, and increased erythroid colony forming capacity in both UT7 and primary cells. Raft induction was associated with F-actin polymerization, which was blocked by Rho kinase inhibition. These data indicate that deficient raft integrity impairs EpoR signaling, and provides a novel strategy to enhance EpoR signal fidelity in non-del(5q) MDS.

Indexed as

ActinsAgedAged, 80 and overAmidesCell Line, TumorDrug Evaluation, PreclinicalErythroid Precursor CellsFemaleHumansImmunologic FactorsLenalidomideMaleMembrane MicrodomainsMyelodysplastic SyndromesProtein MultimerizationPyridinesActinsAmidesImmunologic FactorsLenalidomidePyridinesReceptors, Erythropoietinrho-Associated KinasesThalidomideY 27632

Identifiers

PMID25469886
PMCPMC4254997
OpenAlexW2021618009

What OpenQuestion holds

Textmetadata
LicenceCC BY
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 OpenQuestion graph.