Evidence map›Paper›PMID 39803492›Full record

ArticlebioRxiv : the preprint server for biology2024

CEBPA repression by MECOM blocks differentiation to drive aggressive leukemias.

Travis J Fleming, Mateusz Antoszewski, Sander Lambo, Michael C Gundry, Riccardo Piussi, Lara Wahlster, Sanjana Shah, Fiona E Reed, Kevin D Dong, Joao A Paulo and 14 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors.

Travis J FlemingDivision of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Mateusz AntoszewskiDivision of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Sander LamboDivision of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Michael C GundryDivision of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Riccardo PiussiDivision of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Lara WahlsterDivision of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Sanjana ShahDivision of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Fiona E ReedDivision of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Kevin D DongDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Joao A PauloDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0002-4291-413X
Steven P GygiDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Claudia MimosoDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, 02115, USA.
Seth R GoldmanDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, 02115, USA.
Karen AdelmanDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, 02115, USA.
Jennifer A PerryDivision of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Yana PikmanDivision of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Kimberly StegmaierDivision of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Maria N BarrachinaVascular Biology Program, Boston Children's Hospital, Boston, MA 02115, USA.
Kellie R MachlusVascular Biology Program, Boston Children's Hospital, Boston, MA 02115, USA.
Volker HovestadtDivision of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Andrea ArrudaPrincess Margaret Cancer Centre, University Health Network, Toronto, Canada.
Mark D MindenPrincess Margaret Cancer Centre, University Health Network, Toronto, Canada.
Richard A VoitDivision of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Vijay G SankaranDivision of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0003-0044-443X

Funding

Systematic Genetic Dissection of Human ErythropoiesisR01DK103794 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI Vijay Ganesh Sankaran · 2014 to 2026
$5.9M
Next generation functional genomics of hematology traitsR01HL146500 · NHLBI · UNIVERSITY OF WASHINGTON · PI ALEXANDER P REINER · 2020 to 2026
$5.7M
Targeting Pediatric Cancer VulnerabilitiesR35CA283977 · NCI · DANA-FARBER CANCER INST · PI Kimberly Stegmaier · 2023 to 2026
$4.2M
Selective pressures from inherited variation impacting myeloproliferative neoplasm initiationR01CA265726 · NCI · BOSTON CHILDREN'S HOSPITAL · PI Vijay Ganesh Sankaran · 2022 to 2026
$2.5M
Variant to Function Mapping of B-ALL Risk LociR01CA292941 · NCI · BOSTON CHILDREN'S HOSPITAL · PI Adam De Smith, Vijay Ganesh Sankaran · 2024 to 2026
$2.0M
Clonal analysis of cancer by mitochondrial DNA barcodingR33CA278393 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI SANKARAN, VIJAY GANESH, VAN GALEN, PETER · 2023 to 2025
$1.3M
Uncovering therapeutic vulnerabilities in AML through mechanistic interrogation of MECOM activityK08CA286756 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI Richard A Voit · 2024 to 2026
$687k
Functionally dissecting MECOM gene regulation in high-risk leukemiaF31CA287658 · NCI · HARVARD MEDICAL SCHOOL · PI FLEMING, TRAVIS J · 2024 to 2025
$81k
NCI NIH HHS F31 CA287658NCI NIH HHS K08 CA286756NCI NIH HHS R01 CA265726NCI NIH HHS R01 CA292941NCI NIH HHS R33 CA278393NCI NIH HHS R35 CA283977NHLBI NIH HHS R01 HL146500NIDDK NIH HHS R01 DK103794
6 · The paper itself

Abstract

Acute myeloid leukemias (AMLs) have an overall poor prognosis with many high-risk cases co-opting stem cell gene regulatory programs, yet the mechanisms through which this occurs remain poorly understood. Increased expression of the stem cell transcription factor, MECOM, underlies one key driver mechanism in largely incurable AMLs. How MECOM results in such aggressive AML phenotypes remains unknown. To address existing experimental limitations, we engineered and applied targeted protein degradation with functional genomic readouts to demonstrate that MECOM promotes malignant stem cell-like states by directly repressing pro-differentiation gene regulatory programs. Remarkably and unexpectedly, a single node in this network, a MECOM-bound

Identifiers

PMID39803492
PMCPMC11722404

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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.