Evidence map›Paper›PMID 35590143›Full record

ArticleMed (New York, N.Y.)2022

JAK inhibition in a patient with a STAT1 gain-of-function variant reveals STAT1 dysregulation as a common feature of aplastic anemia.

Jacob M Rosenberg, Joshua M Peters, Travis Hughes, Caleb A Lareau, Leif S Ludwig, Lucas R Massoth, Christina Austin-Tse, Heidi L Rehm, Bryan Bryson, Yi-Bin Chen and 4 more

Registry-linked trialOpen access · greenAbstract readCase Reports
PubMed Full text at PMC Publisher
In one paragraph

Article in Med (New York, N.Y.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03906318 (Expanded Access Use of Itacitinib to Treat a Single Patient With Aplastic Anemia), which is not on this map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
3.2field-weighted citation impact, top 7% 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.

NCT03906318 no longer availablenot on this map

Expanded Access Use of Itacitinib to Treat a Single Patient With Aplastic Anemia

Typeexpanded_accessSponsorIncyte CorporationConditionsAplastic AnemiaArmsIticitinib
3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 23 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

14 authors at 4 institutions in 1 country.

Jacob M RosenbergDepartment of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA; Harvard T.H. Chan School of Public Health, Boston, MA, USA. Electronic address: jrosenberg2@mgh.harvard.edu.
Joshua M PetersRagon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Travis HughesRagon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA; Institute for Medical Engineering and Science, Department of Chemistry, and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Caleb A LareauHarvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Leif S LudwigHarvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Lucas R MassothHarvard Medical School, Boston, MA, USA; Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.
Christina Austin-TseDepartment of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA; Laboratory for Molecular Medicine, Partners Personalized Medicine, Cambridge, MA, USA; Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.
Heidi L RehmDepartment of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA; Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.
Bryan BrysonRagon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Institute for Medical Engineering and Science, Department of Chemistry, and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Yi-Bin ChenDepartment of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Massachusetts General Hospital Cancer Center, Boston, MA, USA.
Aviv RegevBroad Institute of MIT and Harvard, Cambridge, MA, USA; Genentech, South San Francisco, CA, USA.
Alex K ShalekRagon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA; Institute for Medical Engineering and Science, Department of Chemistry, and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Sarah M FortuneRagon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA; Harvard T.H. Chan School of Public Health, Boston, MA, USA.
David B SykesDepartment of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Center for Regenerative Medicine, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; Harvard Stem Cell Institute, Cambridge, MA, USA; Massachusetts General Hospital Cancer Center, Boston, MA, USA. Electronic address: dbsykes@mgh.harvard.edu.
Broad Institute · USHarvard University · USMassachusetts General Hospital · USRagon Institute of MGH, MIT and Harvard · US

Funding

Multidisciplinary HIV Training ProgramT32AI007387 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI Daniel R. Kuritzkes · 1990 to 2026
$8.8M
NIAID NIH HHS T32 AI007387
6 · The paper itself

Abstract

backgroundIdiopathic aplastic anemia is a potentially lethal disease, characterized by T cell-mediated autoimmune attack of bone marrow hematopoietic stem cells. Standard of care therapies (stem cell transplantation or immunosuppression) are effective but associated with a risk of serious toxicities.

methodsAn 18-year-old man presented with aplastic anemia in the context of a germline gain-of-function variant in STAT1. Treatment with the JAK1 inhibitor itacitinib resulted in a rapid resolution of aplastic anemia and a sustained recovery of hematopoiesis. Peripheral blood and bone marrow samples were compared before and after JAK1 inhibitor therapy.

findingsFollowing therapy, samples showed a decrease in the plasma concentration of interferon-γ, a decrease in PD1-positive exhausted CD8

conclusionsThese findings raise the possibility that STAT1 hyperactivition defines a subset of idiopathic aplastic anemia patients for whom JAK inhibition may be an efficacious therapy.

fundingFunding was provided by the Massachusetts General Hospital Department of Medicine Pathways Program and NIH T32 AI007387. A trial registration is at https://clinicaltrials.gov/ct2/show/NCT03906318.

Indexed as

Anemia, AplasticJanus Kinase InhibitorsAcetonitrilesAdolescentCD8-Positive T-LymphocytesGain of Function MutationHumansMalePyrazolesPyrimidinesPyrrolesSTAT1 Transcription FactorAcetonitrilesitacitinibJanus Kinase InhibitorsPyrazolesPyrimidinesPyrrolesSTAT1 protein, humanSTAT1 Transcription FactorAplastic anemiaautoimmuneinterferon gammaitacitinibJAK inhibitionJAK/STATSTAT1 gain-of-functionSTAT1 GOFT-cell exhaustionTranslation to patients

Identifiers

PMID35590143
PMCPMC9123284
OpenAlexW4213026812

What OpenQuestion holds

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Registered trials

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.