Evidence map›Paper›PMID 39354203›Full record

ArticleLeukemia2025

The epigenetic state of the cell of origin defines mechanisms of leukemogenesis.

Zhiheng Li, Sara Fierstein, Mayuri Tanaka-Yano, Katie Frenis, Chun-Chin Chen, Dahai Wang, Marcelo Falchetti, Parker Côté, Christina Curran, Kate Lu and 7 more

Abstract read
PubMed Publisher
In one paragraph

Article in Leukemia, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Review
  2. Article
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

17 authors.

Zhiheng LiStem Cell Program and Stem Cell Transplantation Programs, Boston Children's Hospital, Boston, MA, USA.
Sara FiersteinStem Cell Program and Stem Cell Transplantation Programs, Boston Children's Hospital, Boston, MA, USA.ORCID 0000-0002-3192-6530
Mayuri Tanaka-YanoStem Cell Program and Stem Cell Transplantation Programs, Boston Children's Hospital, Boston, MA, USA.ORCID 0000-0001-6309-3273
Katie FrenisStem Cell Program and Stem Cell Transplantation Programs, Boston Children's Hospital, Boston, MA, USA.ORCID 0000-0003-4103-0882
Chun-Chin ChenStem Cell Program and Stem Cell Transplantation Programs, Boston Children's Hospital, Boston, MA, USA.
Dahai WangStem Cell Program and Stem Cell Transplantation Programs, Boston Children's Hospital, Boston, MA, USA.
Marcelo FalchettiFederal University of Santa Catarina, Florianopolis, Brazil.ORCID 0000-0002-9438-680X
Parker CôtéMassachusetts Institute of Technology, Cambridge, MA, USA.
Christina CurranStem Cell Program and Stem Cell Transplantation Programs, Boston Children's Hospital, Boston, MA, USA.
Kate LuMassachusetts Institute of Technology, Cambridge, MA, USA.
Tianxin LiuDepartment of Hematology/Oncology, Boston Children's Hospital, Boston, MA, USA.
Stuart OrkinDepartment of Hematology/Oncology, Boston Children's Hospital, Boston, MA, USA.
Hojun LiMassachusetts Institute of Technology, Cambridge, MA, USA.
Edroaldo Lummertz da RochaFederal University of Santa Catarina, Florianopolis, Brazil.ORCID 0000-0003-0537-4223
Shaoyan HuDepartment of Hematology/Oncology, Children's Hospital of Soochow University, Suzhou, Jiangsu, China. hushaoyan@suda.edu.cn.ORCID 0000-0002-3386-6957
Qian Zhu *Baylor College of Medicine, Department of Molecular and Human Genetics, Houston, TX, USA. qian.zhu@bcm.edu.ORCID 0000-0001-7062-8221
R Grant Rowe *Stem Cell Program and Stem Cell Transplantation Programs, Boston Children's Hospital, Boston, MA, USA. Grant_rowe@dfci.harvard.edu.ORCID 0000-0003-3620-2950

Funding

Regulating proliferation and differentiation of erythroid progenitorsK08DK123414 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LI, HOJUN · 2020 to 2024
$828k
NIDDK NIH HHS K08 DK123414V Foundation for Cancer Research (V Foundation) V2022-01
6 · The paper itself

Abstract

Acute myeloid leukemia (AML) shows variable clinical outcome. The normal hematopoietic cell of origin impacts the clinical behavior of AML, with AML from hematopoietic stem cells (HSCs) prone to chemotherapy resistance in model systems. However, the mechanisms by which HSC programs are transmitted to AML are not known. Here, we introduce the leukemogenic MLL-AF9 translocation into defined human hematopoietic populations, finding that AML from HSCs is enriched for leukemic stem cells (LSCs) compared to AML from progenitors. By epigenetic profiling, we identify a putative inherited program from the normal HSC that collaborates with oncogene-driven programs to confer aggressive behavior in HSC-AML. We find that components of this program are required for HSC-AML growth and survival and identify RNA polymerase (RNAP) II-mediated transcription as a therapeutic vulnerability. Overall, we propose a mechanism as to how epigenetic programs from the leukemic cell of origin are inherited through transformation to impart the clinical heterogeneity of AML.

Indexed as

Epigenesis, GeneticHematopoietic Stem CellsLeukemia, Myeloid, AcuteAnimalsCarcinogenesisCell Transformation, NeoplasticGene Expression Regulation, LeukemicHumansMiceMyeloid-Lymphoid Leukemia ProteinNeoplastic Stem CellsOncogene Proteins, FusionMLL-AF9 fusion protein, humanMyeloid-Lymphoid Leukemia ProteinOncogene Proteins, Fusion

Identifiers

PMID39354203

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.