Evidence map›Paper›PMID 38007585›Full record

ArticleLeukemia2024

TP-0184 inhibits FLT3/ACVR1 to overcome FLT3 inhibitor resistance and hinder AML growth synergistically with venetoclax.

Anudishi Tyagi, Appalaraju Jaggupilli, Stanley Ly, Bin Yuan, Fouad El-Dana, Venkatesh L Hegde, Vivek Anand, Bijender Kumar, Mamta Puppala, Zheng Yin and 8 more

Open access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Leukemia, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.6field-weighted citation impact, top 26% 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

6 citing papers in PubMed, 2 citations in OpenAlex.

  1. Review
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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

18 authors at 4 institutions in 1 country.

Anudishi TyagiSection of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Appalaraju JaggupilliSection of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Stanley LySection of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Bin YuanSection of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Fouad El-DanaSection of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Venkatesh L HegdeSection of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Vivek AnandSection of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Bijender KumarDepartment of Stem Cell Transplantation, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Mamta PuppalaDepartment of Systems Medicine and Bioengineering, Houston Methodist Neal Cancer Center, Weill Cornell Medicine, Houston, TX, USA.
Zheng YinDepartment of Systems Medicine and Bioengineering, Houston Methodist Neal Cancer Center, Weill Cornell Medicine, Houston, TX, USA.
Stephen T C WongDepartment of Systems Medicine and Bioengineering, Houston Methodist Neal Cancer Center, Weill Cornell Medicine, Houston, TX, USA.ORCID http://orcid.org/0000-0001-9188-6502
Alexis MollardUniversity of Utah, Huntsman Cancer Institute, Salt Lake City, UT, USA.
Hariprasad VankayalapatiUniversity of Utah, Huntsman Cancer Institute, Salt Lake City, UT, USA.ORCID http://orcid.org/0000-0002-5477-2124
Jason M FoulksSumitomo Pharma Oncology, Inc, Lehi, UT, USA.
Steven L WarnerSumitomo Pharma Oncology, Inc, Lehi, UT, USA.
Naval DaverSection of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0001-7103-373X
Gautam BorthakurSection of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0001-7679-6453
V Lokesh BattulaSection of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. vbattula@mdanderson.org.ORCID http://orcid.org/0000-0001-5415-9058
The University of Texas MD Anderson Cancer Center · USHouston Methodist · USSumitomo Dainippon Pharma (United States) · USUniversity of Utah · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

We identified activin A receptor type I (ACVR1), a member of the TGF-β superfamily, as a factor favoring acute myeloid leukemia (AML) growth and a new potential therapeutic target. ACVR1 is overexpressed in FLT3-mutated AML and inhibition of ACVR1 expression sensitized AML cells to FLT3 inhibitors. We developed a novel ACVR1 inhibitor, TP-0184, which selectively caused growth arrest in FLT3-mutated AML cell lines. Molecular docking and in vitro kinase assays revealed that TP-0184 binds to both ACVR1 and FLT3 with high affinity and inhibits FLT3/ACVR1 downstream signaling. Treatment with TP-0184 or in combination with BCL2 inhibitor, venetoclax dramatically inhibited leukemia growth in FLT3-mutated AML cell lines and patient-derived xenograft models in a dose-dependent manner. These findings suggest that ACVR1 is a novel biomarker and plays a role in AML resistance to FLT3 inhibitors and that FLT3/ACVR1 dual inhibitor TP-0184 is a novel potential therapeutic tool for AML with FLT3 mutations.

Indexed as

Leukemia, Myeloid, AcuteActivin Receptors, Type IApoptosisBridged Bicyclo Compounds, HeterocyclicCell Line, Tumorfms-Like Tyrosine Kinase 3HumansMolecular Docking SimulationMutationProtein Kinase InhibitorsSulfonamidesActivin Receptors, Type IACVR1 protein, humanBridged Bicyclo Compounds, HeterocyclicFLT3 protein, humanfms-Like Tyrosine Kinase 3Protein Kinase InhibitorsSulfonamidesvenetoclax

Identifiers

PMID38007585
OpenAlexW4389002701

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.