Evidence map›Paper›PMID 21263155›Full record

ArticleBlood2011

FLT3 ligand impedes the efficacy of FLT3 inhibitors in vitro and in vivo.

Takashi Sato, Xiaochuan Yang, Steven Knapper, Paul White, B Douglas Smith, Steven Galkin, Donald Small, Alan Burnett, Mark Levis

Open access · bronzeAbstract readEvaluation Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Blood, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 159 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
159citing papers in PubMed, 1 pooled it
13.5field-weighted citation impact, top 1% 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

159 citing papers in PubMed, 1 synthesis or guideline pooled it, 257 citations in OpenAlex.

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  13. FLT3-Mutated AML: Transplanting with Precision in the Targeted Era.Current hematologic malignancy reports · 2026
    Review
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  18. Acute Myeloid Leukemia With a Non-CanonicalJournal of medical cases · 2026
    Article
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99 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 2 countries.

Takashi SatoSidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231, USA.
Xiaochuan Yang
Steven Knapper
Paul White
B Douglas Smith
Steven Galkin
Donald Small
Alan Burnett
Mark Levis
Sidney Kimmel Comprehensive Cancer Center · USCardiff University · GB

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI Rosalie Wollett · 1985 to 2026
$208.6M
University of Texas M.D. Anderson Cancer SPORE-LeukemiaP50CA100632 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI KONOPLEVA, MARINA Y · 2003 to 2023
$43.7M
FLT3 Tyrosine Kinase Inhibitors As Therapy for LeukemiaR01CA090668 · NCI · JOHNS HOPKINS UNIVERSITY · PI SMALL, DONALD · 2002 to 2018
$5.0M
Incorporating FLT3 inhibitors into AML treatment regimensR01CA128864 · NCI · JOHNS HOPKINS UNIVERSITY · PI LEVIS, MARK J · 2008 to 2012
$1.7M
Cancer Research UK 9948NCI NIH HHS 2 P30 CA 006973-44NCI NIH HHS P30 CA006973NCI NIH HHS P50 CA100632NCI NIH HHS P50 CA100632-06NCI NIH HHS R01 CA090668NCI NIH HHS R01 CA128864
6 · The paper itself

Abstract

We examined in vivo FLT3 inhibition in acute myeloid leukemia patients treated with chemotherapy followed by the FLT3 inhibitor lestaurtinib, comparing newly diagnosed acute myeloid leukemia patients with relapsed patients. Because we noted that in vivo FLT3 inhibition by lestaurtinib was less effective in the relapsed patients compared with the newly diagnosed patients, we investigated whether plasma FLT3 ligand (FL) levels could influence the efficacy of FLT3 inhibition in these patients. After intensive chemotherapy, FL levels rose to a mean of 488 pg/mL on day 15 of induction therapy for newly diagnosed patients, whereas they rose to a mean of 1148 pg/mL in the relapsed patients. FL levels rose even higher with successive courses of chemotherapy, to a mean of 3251 pg/mL after the fourth course. In vitro, exogenous FL at concentrations similar to those observed in patients mitigated FLT3 inhibition and cytotoxicity for each of 5 different FLT3 inhibitors (lestaurtinib, midostaurin, sorafenib, KW-2449, and AC220). The dramatic increase in FL level after chemotherapy represents a possible obstacle to inhibiting FLT3 in this clinical setting. These findings could have important implications regarding the design and outcome of trials of FLT3 inhibitors and furthermore suggest a rationale for targeting FL as a therapeutic strategy.

Indexed as

Antineoplastic AgentsBenzenesulfonatesCarbazolesCells, CulturedDrug Antagonismfms-Like Tyrosine Kinase 3FuransHumansIndazolesInhibitory Concentration 50Leukemia, Myeloid, AcuteMembrane ProteinsMulticenter Studies as TopicNiacinamidePhenylurea CompoundsPiperazinesAntineoplastic AgentsBenzenesulfonatesCarbazolesflt3 ligand proteinFLT3 protein, humanfms-Like Tyrosine Kinase 3FuransIndazolesKW 2449lestaurtinibMembrane ProteinsmidostaurinNiacinamidePhenylurea CompoundsPiperazinesProtein Kinase InhibitorsPyridinesSorafenibStaurosporine

Identifiers

PMID21263155
PMCPMC3069670
OpenAlexW1981811959

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.