Evidence map›Paper›PMID 18945969›Full record

ArticleBlood2009

Stroma-dependent apoptosis in clonal hematopoietic precursors correlates with expression of PYCARD.

Andrew J Mhyre, A Mario Marcondes, Emily Y Spaulding, H Joachim Deeg

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 1 pooled it
1.5field-weighted citation impact, top 18% 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

22 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.

  1. Pooled it
  2. Article
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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

4 authors at 1 institution in 1 country.

Andrew J MhyreClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
A Mario Marcondes
Emily Y Spaulding
H Joachim Deeg
Fred Hutch Cancer Center · US

Funding

Cell Death and Clonal Survival in Myelodysplastic Syndr*R01HL082941 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI DEEG, H. JOACHIM · 2005 to 2008
$1.7M
NHLBI NIH HHS HL082941NHLBI NIH HHS R01 HL082941
6 · The paper itself

Abstract

The role of the marrow microenvironment in the pathophysiology of myelodysplastic syndromes (MDSs) remains controversial. Using stromal/hematopoietic cell cocultures, we investigated the effects of stroma-derived signals on apoptosis sensitivity in hematopoietic precursors. The leukemia-derived cell line KG1a is resistant to proapoptotic ligands. However, when cocultured with the human stromal cell line HS5 (derived from normal marrow) and exposed to tumor necrosis factor-alpha (TNF-alpha), KG1a cells showed caspase-3 activation and induction of apoptosis. Apoptosis was contact dependent. Identical results were obtained in coculture with primary stroma. Gene-expression profiling of KG1a cells identified coculture-induced up-regulation of various genes involved in apoptosis, including PYCARD. Suppression of PYCARD expression in KG1a by miRNA interfered with apoptosis. Knockdown of the TNF receptor 1 (TNFR1) or TNFR2 in HS5 cells had no effect. However, knockdown of R1 in KG1a cells prevented TNF-alpha-induced apoptosis, while apoptosis was still induced by TNF-alpha-related apoptosis-inducing ligand. Primary CD34(+) cells from MDS marrow, when cocultured with HS5 and TNF-alpha, also underwent apoptosis. In contrast, no apoptosis was observed in CD34(+) cells from the marrow of healthy donors. These data indicate that stroma may convey not only protective effects on hematopoietic cells, but, dependent upon the milieu, may also facilitate apoptosis.

Indexed as

ApoptosisBlotting, WesternCARD Signaling Adaptor ProteinsCaspase 3Cell CommunicationCell LineCoculture TechniquesCytoskeletal ProteinsGene ExpressionHematopoietic Stem CellsHumansMyelodysplastic SyndromesReceptors, Tumor Necrosis FactorReverse Transcriptase Polymerase Chain ReactionRNA InterferenceStromal CellsCARD Signaling Adaptor ProteinsCaspase 3Cytoskeletal ProteinsPYCARD protein, humanReceptors, Tumor Necrosis FactorTNF-Related Apoptosis-Inducing LigandTumor Necrosis Factor-alpha

Identifiers

PMID18945969
PMCPMC2628371
OpenAlexW2053981824

What OpenQuestion holds

Textmetadata
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.