Evidence map›Paper›PMID 27671675›Full record

ArticleCancer research2016

FGF2 from Marrow Microenvironment Promotes Resistance to FLT3 Inhibitors in Acute Myeloid Leukemia.

Elie Traer, Jacqueline Martinez, Nathalie Javidi-Sharifi, Anupriya Agarwal, Jennifer Dunlap, Isabel English, Tibor Kovacsovics, Jeffrey W Tyner, Melissa Wong, Brian J Druker

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
95citing papers in PubMed, 1 pooled it
8.0field-weighted citation impact, top 2% 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

95 citing papers in PubMed, 1 synthesis or guideline pooled it, 155 citations in OpenAlex.

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  20. Targeting CCL2/CCR2 Signaling Overcomes MEK Inhibitor Resistance in Acute Myeloid Leukemia.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024
    Article

35 more citing papers are in PubMed but not listed here.

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

10 authors at 1 institution in 1 country.

Elie TraerKnight Cancer Institute, Oregon Health and Science University, Portland, Oregon. traere@ohsu.edu.
Jacqueline MartinezKnight Cancer Institute, Oregon Health and Science University, Portland, Oregon.
Nathalie Javidi-SharifiKnight Cancer Institute, Oregon Health and Science University, Portland, Oregon.
Anupriya AgarwalKnight Cancer Institute, Oregon Health and Science University, Portland, Oregon.
Jennifer DunlapKnight Cancer Institute, Oregon Health and Science University, Portland, Oregon.
Isabel EnglishKnight Cancer Institute, Oregon Health and Science University, Portland, Oregon.
Tibor KovacsovicsBMT, Blood and Marrow Transplant, Huntsman Cancer Institute, Salt Lake City, Utah.
Jeffrey W TynerKnight Cancer Institute, Oregon Health and Science University, Portland, Oregon.
Melissa WongKnight Cancer Institute, Oregon Health and Science University, Portland, Oregon.
Brian J DrukerKnight Cancer Institute, Oregon Health and Science University, Portland, Oregon.
Howard Hughes Medical Institute · US

Funding

Oregon Clinical and Translational Research InstituteKL2TR000152 · NCATS · OREGON HEALTH & SCIENCE UNIVERSITY · PI ELLISON, DAVID H · 2012 to 2015
$1.7M
Howard Hughes Medical InstituteNCATS NIH HHS KL2 TR000152
6 · The paper itself

Abstract

Potent FLT3 inhibitors, such as quizartinib (AC220), have shown promise in treating acute myeloid leukemia (AML) containing FLT3 internal tandem duplication (ITD) mutations. However, responses are not durable and resistance develops within months. In this study, we outline a two-step model of resistance whereby extrinsic microenvironmental proteins FLT3 ligand (FL) and fibroblast growth factor 2 (FGF2) protect FLT3-ITD+ MOLM14 cells from AC220, providing time for subsequent accumulation of ligand-independent resistance mechanisms. FL directly attenuated AC220 inhibition of FLT3, consistent with previous reports. Conversely, FGF2 promoted resistance through activation of FGFR1 and downstream MAPK effectors; these resistant cells responded synergistically to combinatorial inhibition of FGFR1 and FLT3. Removing FL or FGF2 from ligand-dependent resistant cultures transiently restored sensitivity to AC220, but accelerated acquisition of secondary resistance via reactivation of FLT3 and RAS/MAPK signaling. FLT3-ITD AML patients treated with AC220 developed increased FGF2 expression in marrow stromal cells, which peaked prior to overt clinical relapse and detection of resistance mutations. Overall, these results support a strategy of early combination therapy to target early survival signals from the bone marrow microenvironment, in particular FGF2, to improve the depth of response in FLT3-ITD AML. Cancer Res; 76(22); 6471-82. ©2016 AACR.

Indexed as

Cell Line, TumorFibroblast Growth Factor 2fms-Like Tyrosine Kinase 3HumansLeukemia, Myeloid, AcuteTumor MicroenvironmentFibroblast Growth Factor 2fms-Like Tyrosine Kinase 3

Identifiers

PMID27671675
PMCPMC5290120
OpenAlexW2526397866

What OpenQuestion holds

Textmetadata
LicenceTDM
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.