Evidence map›Paper›PMID 19336761›Full record

ArticleBlood2009

Long-term polyclonal and multilineage engraftment of methylguanine methyltransferase P140K gene-modified dog hematopoietic cells in primary and secondary recipients.

Brian C Beard, Reeteka Sud, Kirsten A Keyser, Christina Ironside, Tobias Neff, Sabine Gerull, Grant D Trobridge, Hans-Peter Kiem

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 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.5field-weighted citation impact, top 10% 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

20 citing papers in PubMed, 28 citations in OpenAlex.

  1. Article
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  5. Gene Addition Strategies for β-Thalassemia and Sickle Cell Anemia.Advances in experimental medicine and biology · 2017
    Review
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  18. Review
  19. Article
  20. Recent advances in lentiviral vector development and applications.Molecular therapy : the journal of the American Society of Gene Therapy · 2010
    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

8 authors at 1 institution in 1 country.

Brian C BeardFred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
Reeteka Sud
Kirsten A Keyser
Christina Ironside
Tobias Neff
Sabine Gerull
Grant D Trobridge
Hans-Peter Kiem
Fred Hutch Cancer Center · US

Funding

UNRELATED AND HLA-MISMATCHED RELATED DONOR TRANSPLANTSP01HL036444 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI RAWLINGS, DAVID J · 1986 to 2010
$25.9M
CORE--VECTOR PRODUCTIONP30DK056465 · NIDDK · FRED HUTCHINSON CANCER RESEARCH CENTER · PI HEIMFELD, SHELLY · 1999 to 2014
$14.9M
PILOT STUDY--RETROVIRUS MEDIATED TRANSFER OF HUMAN GLUCOCEREBROSIDASE GENEP30DK047754 · NIDDK · UNIVERSITY OF WASHINGTON · PI MILLER, ARTHUR DUSTY · 1994 to 2008
$8.4M
LAGLIDADG Delivery and Gene Repair in Hematopoietic Stem Cells (7 of 11)RL1HL092554 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI KIEM, HANS-PETER · 2007 to 2011
$3.1M
MGMT-Mediated in vivo Selection in a Large Animal ModelR01HL074162 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI KIEM, HANS-PETER · 2003 to 2006
$1.7M
NHLBI NIH HHS HL092554NHLBI NIH HHS HL36444NHLBI NIH HHS HL74162NHLBI NIH HHS P01 HL036444NHLBI NIH HHS R01 HL074162NHLBI NIH HHS RL1 HL092554NIDDK NIH HHS DK47754NIDDK NIH HHS DK56465NIDDK NIH HHS P30 DK047754NIDDK NIH HHS P30 DK056465
6 · The paper itself

Abstract

Overexpression of methylguanine methyltransferase P140K (MGMTP140K) has been successfully used for in vivo selection and chemoprotection in mouse and large animal studies, and has promise for autologous and allogeneic gene therapy. We examined the long-term safety of MGMTP140K selection in a clinically relevant dog model. Based on the association of provirus integration and proto-oncogene activation leading to leukemia in the X-linked immunodeficiency trial, we focused our analysis on the distribution of retrovirus integration sites (RIS) relative to proto-oncogene transcription start sites (TSS). We analyzed RIS near proto-oncogene TSS before (n = 157) and after (n = 129) chemotherapy in dogs that received MGMTP140K gene-modified cells and identified no overall increase of RIS near proto-oncogene TSS after chemotherapy. We also wanted to determine whether in vivo selected cells retained fundamental characteristics of hematopoietic stem cells. To that end, we performed secondary transplantation of MGMTP140K gene-modified cells after in vivo selection in dog leukocyte antigen (DLA)-matched dogs. Gene-modified cells achieved multilineage repopulation, and we identified the same gene-modified clone in both dogs more than 800 and 900 days after transplantation. These data suggest that MGMTP140K selection is well tolerated and should allow clinically for selection of gene-corrected cells in genetic or infectious diseases or chemoprotection for treatment of malignancy.

Indexed as

Graft SurvivalHematopoietic Stem Cell TransplantationAnimalsCell LineageDogsGenetic TherapyGenetic VectorsHematopoietic Stem CellsO(6)-Methylguanine-DNA MethyltransferaseRetroviridaeO(6)-Methylguanine-DNA Methyltransferase

Identifiers

PMID19336761
PMCPMC2686180
OpenAlexW2029660607

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.