Evidence map›Paper›PMID 21123823›Full record

ArticleBlood2011

Knockdown of Hspa9, a del(5q31.2) gene, results in a decrease in hematopoietic progenitors in mice.

Tim H-P Chen, Amal Kambal, Kilannin Krysiak, Mark A Walshauser, Gagan Raju, Justin F Tibbitts, Matthew J Walter

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
1.6field-weighted citation impact, top 16% 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

29 citing papers in PubMed, 55 citations in OpenAlex.

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  11. The Role of Somatic Mutations in Acute Myeloid Leukemia Pathogenesis.Cold Spring Harbor perspectives in medicine · 2021
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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

7 authors at 1 institution in 1 country.

Tim H-P ChenDepartment of Medicine, Division of Oncology, Washington University School of Medicine, 660 South Euclid Ave., St Louis, MO 63110, USA.
Amal Kambal
Kilannin Krysiak
Mark A Walshauser
Gagan Raju
Justin F Tibbitts
Matthew J Walter
Washington University in St. Louis · US

Funding

Washington University Center for Cellular ImagingP30CA091842 · NCI · WASHINGTON UNIVERSITY · PI TIMOTHY J. EBERLEIN · 2001 to 2026
$128.0M
MOLECULAR ONCOLOGY TRAINING GRANTT32CA113275 · NCI · WASHINGTON UNIVERSITY · PI Matthew J Walter · 2006 to 2026
$5.7M
Genomics of myelodysplastic syndromesR01HL082973 · NHLBI · WASHINGTON UNIVERSITY · PI GRAUBERT, TIMOTHY A · 2005 to 2008
$2.1M
Howard Hughes Medical InstituteNCI NIH HHS P30 CA091842NCI NIH HHS T32 CA113275NHLBI NIH HHS HL082973NHLBI NIH HHS R01 HL082973
6 · The paper itself

Abstract

Heterozygous deletions spanning chromosome 5q31.2 occur frequently in the myelodysplastic syndromes (MDS) and are highly associated with progression to acute myeloid leukemia (AML) when p53 is mutated. Mutagenesis screens in zebrafish and mice identified Hspa9 as a del(5q31.2) candidate gene that may contribute to MDS and AML pathogenesis, respectively. To test whether HSPA9 haploinsufficiency recapitulates the features of ineffective hematopoiesis observed in MDS, we knocked down the expression of HSPA9 in primary human hematopoietic cells and in a murine bone marrow-transplantation model using lentivirally mediated gene silencing. Knockdown of HSPA9 in human cells significantly delayed the maturation of erythroid precursors, but not myeloid or megakaryocytic precursors, and suppressed cell growth by 6-fold secondary to an increase in apoptosis and a decrease in the cycling of cells compared with control cells. Erythroid precursors, B lymphocytes, and the bone marrow progenitors c-kit(+)/lineage(-)/Sca-1(+) (KLS) and megakaryocyte/erythrocyte progenitor (MEP) were significantly reduced in a murine Hspa9-knockdown model. These abnormalities suggest that cooperating gene mutations are necessary for del(5q31.2) MDS cells to gain clonal dominance in the bone marrow. Our results demonstrate that Hspa9 haploinsufficiency alters the hematopoietic progenitor pool in mice and contributes to abnormal hematopoiesis.

Indexed as

Chromosome DeletionAnimalsApoptosisBlotting, WesternBone Marrow CellsCarrier ProteinsCells, CulturedChromosomes, MammalianFetal BloodFlow CytometryHaploinsufficiencyHematopoietic Stem CellsHematopoietic SystemHSP70 Heat-Shock ProteinsHumansMiceCarrier ProteinsHSP70 Heat-Shock ProteinsHspa9 protein, mouseTumor Suppressor Protein p53

Identifiers

PMID21123823
PMCPMC3056590
OpenAlexW2082855967

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.