Evidence mapPaperPMID 35804097Full record

ArticleLeukemia2022

GFI1B acts as a metabolic regulator in hematopoiesis and acute myeloid leukemia.

Longlong Liu, Pradeep Kumar Patnana, Xiaoqing Xie, Daria Frank, Subbaiah Chary Nimmagadda, Minhua Su, Donghua Zhang, Thorsten Koenig, Frank Rosenbauer, Marie Liebmann and 9 more

Open access · hybridAbstract read
In one paragraph

Article in Leukemia, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
3.5field-weighted citation impact, top 6% 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

12 citing papers in PubMed, 24 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

19 authors at 6 institutions in 2 countries.

Longlong LiuDepartment of Medicine A, Hematology, Oncology and Pneumology, University Hospital Muenster, 48149, Muenster, Germany.
Pradeep Kumar PatnanaDepartment of Medicine A, Hematology, Oncology and Pneumology, University Hospital Muenster, 48149, Muenster, Germany.
Xiaoqing XieDepartment of Medicine A, Hematology, Oncology and Pneumology, University Hospital Muenster, 48149, Muenster, Germany.
Daria FrankDepartment of Medicine A, Hematology, Oncology and Pneumology, University Hospital Muenster, 48149, Muenster, Germany.
Subbaiah Chary NimmagaddaDepartment of Medicine A, Hematology, Oncology and Pneumology, University Hospital Muenster, 48149, Muenster, Germany.
Minhua SuState Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 300052, Tianjin, China.
Donghua ZhangDepartment of Hematology, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, 430030, Wuhan, China.
Thorsten KoenigInstitute of Molecular Tumor Biology, Faculty of Medicine, University of Muenster, 48149, Muenster, Germany.
Frank RosenbauerInstitute of Molecular Tumor Biology, Faculty of Medicine, University of Muenster, 48149, Muenster, Germany.ORCID http://orcid.org/0000-0001-7977-9421
Marie LiebmannDepartment of Neurology with Institute of Translational Neurology, University Hospital Muenster, 48149, Muenster, Germany.
Luisa KlotzDepartment of Neurology with Institute of Translational Neurology, University Hospital Muenster, 48149, Muenster, Germany.
Wendan XuDepartment of Medicine A, Hematology, Oncology and Pneumology, University Hospital Muenster, 48149, Muenster, Germany.
Jan VorwerkDepartment of Medicine A, Hematology, Oncology and Pneumology, University Hospital Muenster, 48149, Muenster, Germany.
Felix NeumannFluorescence Microscopy Facility Muenster (FM)2, Institute of Medical Physics and Biophysics, University of Muenster, 48149, Muenster, Germany.
Jana HüveFluorescence Microscopy Facility Muenster (FM)2, Institute of Medical Physics and Biophysics, University of Muenster, 48149, Muenster, Germany.
Andreas UngerInstitute of Physiology II, University of Muenster, 48149, Muenster, Germany.
Jürgen Günther OkunDepartment of General Pediatrics, Division of Neuropediatrics and Metabolic Medicine, Dietmar-Hopp-Metabolic Center, 69120, Heidelberg, Germany.
Bertram OpalkaDepartment of Hematology and Stem Cell Transplantation, University Hospital Essen, University of Duisburg-Essen, 45147, Essen, Germany.
Cyrus KhandanpourDepartment of Medicine A, Hematology, Oncology and Pneumology, University Hospital Muenster, 48149, Muenster, Germany. Cyrus.Khandanpour@uksh.de.ORCID http://orcid.org/0000-0003-4655-6269
University Hospital Münster · DEInstitute of Molecular Biology · DEChinese Academy of Medical Sciences & Peking Union Medical College · CNImmatics Biotechnologies (Germany) · DETongji Hospital · CNUniversity of Duisburg-Essen · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Recent studies highlighted the role of transcription factors in metabolic regulation during hematopoiesis and leukemia development. GFI1B is a transcriptional repressor that plays a critical role in hematopoiesis, and its expression is negatively related to the prognosis of acute myeloid leukemia (AML) patients. We earlier reported a change in the metabolic state of hematopoietic stem cells upon Gfi1b deletion. Here we explored the role of Gfi1b in metabolism reprogramming during hematopoiesis and leukemogenesis. We demonstrated that Gfi1b deletion remarkably activated mitochondrial respiration and altered energy metabolism dependence toward oxidative phosphorylation (OXPHOS). Mitochondrial substrate dependency was shifted from glucose to fatty acids upon Gfi1b deletion via upregulating fatty acid oxidation (FAO). On a molecular level, Gfi1b epigenetically regulated multiple FAO-related genes. Moreover, we observed that metabolic phenotypes evolved as cells progressed from preleukemia to leukemia, and the correlation between Gfi1b expression level and metabolic phenotype was affected by genetic variations in AML cells. FAO or OXPHOS inhibition significantly impeded leukemia progression of Gfi1b-KO MLL/AF9 cells. Finally, we showed that Gfi1b-deficient AML cells were more sensitive to metformin as well as drugs implicated in OXPHOS and FAO inhibition, opening new potential therapeutic strategies.

Indexed as

HematopoiesisLeukemia, Myeloid, AcuteProto-Oncogene ProteinsRepressor ProteinsHematopoietic Stem CellsHumansMyelodysplastic SyndromesTranscription FactorsGFI1B protein, humanProto-Oncogene ProteinsRepressor ProteinsTranscription Factors

Identifiers

PMID35804097
PMCPMC9417998
OpenAlexW4284971582

What Socratic 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 Socratic graph.