Evidence map›Paper›PMID 25283843›Full record

ArticleLeukemia2015

Hhex regulates Kit to promote radioresistance of self-renewing thymocytes in Lmo2-transgenic mice.

B J Shields, R Alserihi, C Nasa, C Bogue, W S Alexander, M P McCormack

Abstract read
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In one paragraph

Article in Leukemia, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.2field-weighted citation impact, top 12% 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

16 citing papers in PubMed, 21 citations in OpenAlex.

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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

6 authors at 2 institutions in 2 countries.

B J Shields1] Cancer and Haematology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia [2] Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.
R Alserihi1] Cancer and Haematology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia [2] Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.
C NasaCancer and Haematology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
C BogueDepartment of Pediatrics, Yale University School of Medicine, New Haven, CT, USA.
W S Alexander1] Cancer and Haematology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia [2] Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.
M P McCormack1] Cancer and Haematology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia [2] Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.
Walter and Eliza Hall Institute of Medical Research · AUYale University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Lmo2 is an oncogenic transcription factor that is frequently overexpressed in T-cell acute leukemias, in particular poor prognosis early T-cell precursor-like (ETP-) acute lymphoblastic leukemia (ALL). The primary effect of Lmo2 is to cause self-renewal of developing CD4(-)CD8(-) (double negative, DN) T cells in the thymus, leading to serially transplantable thymocytes that eventually give rise to leukemia. These self-renewing thymocytes are intrinsically radioresistant implying that they may be a source of leukemia relapse after therapy. The homeobox transcription factor, Hhex, is highly upregulated in Lmo2-transgenic thymocytes and can phenocopy Lmo2 in inducing thymocyte self-renewal, implying that Hhex may be a key component of the Lmo2-induced self-renewal program. To test this, we conditionally deleted Hhex in the thymi of Lmo2-transgenic mice. Surprisingly, this did not prevent accumulation of DN thymocytes, nor alter the rate of overt leukemia development. However, deletion of Hhex abolished the transplantation capacity of Lmo2-transgenic thymocytes and overcame their radioresistance. We found that Hhex regulates Kit expression in Lmo2-transgenic thymocytes and that abrogation of Kit signaling phenocopied loss of Hhex in abolishing the transplantation capacity and radioresistance of these cells. Thus, targeting the Kit signaling pathway may facilitate the eradication of leukemia-initiating cells in immature T-cell leukemias in which it is expressed.

Indexed as

Gene Expression Regulation, LeukemicAdaptor Proteins, Signal TransducingAnimalsCD4 AntigensCD8 AntigensDisease Models, AnimalGamma RaysGene DeletionHomeodomain ProteinsLIM Domain ProteinsMiceMice, TransgenicPrecursor Cell Lymphoblastic Leukemia-LymphomaPrecursor T-Cell Lymphoblastic Leukemia-LymphomaProto-Oncogene Proteins c-kitRadiation ToleranceAdaptor Proteins, Signal TransducingCD4 AntigensCD8 AntigensHhex protein, mouseHomeodomain ProteinsLIM Domain ProteinsLmo2 protein, mouseProto-Oncogene Proteins c-kitTranscription Factors

Identifiers

PMID25283843
OpenAlexW2030801034

What OpenQuestion holds

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Registered trials

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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.