Evidence map›Paper›PMID 35246156›Full record

ArticleMolecular cancer2022

A novel approach for relapsed/refractory FLT3

Ke-Xin Li, Hui-Yang Wu, Wan-Ying Pan, Meng-Qi Guo, De-Zhi Qiu, Yan-Jie He, Yu-Hua Li, Dong-Hua Yang, Yu-Xian Huang

Erratum issuedOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 34 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed, 1 pooled it
4.6field-weighted citation impact, top 4% 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

34 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.

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  10. CAR-T cell therapy for treatment of acute myeloid leukemia, advances and outcomes.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 2 countries.

Ke-Xin Li *Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, Guangdong, China.
Hui-Yang Wu *Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, Guangdong, China.
Wan-Ying PanDepartment of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, Guangdong, China.
Meng-Qi GuoDepartment of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, Guangdong, China.
De-Zhi QiuDepartment of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, Guangdong, China.
Yan-Jie HeDepartment of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, Guangdong, China.
Yu-Hua LiDepartment of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, Guangdong, China.
Dong-Hua YangDepartment of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA. yangd1@stjohns.edu.
Yu-Xian HuangDepartment of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, Guangdong, China. hyx6610@163.com.
Zhujiang Hospital · CNSouthern Medical University · CNSt. John's University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPatients with relapsed/refractory acute myeloid leukaemia (AML) with FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) have limited treatment options and poor prognosis. Therefore, novel treatment modalities are needed. Since high expression of natural killer group 2 member D ligands (NKG2DLs) can be induced by FLT3 inhibitors, we constructed dual-target FLT3 single-chain fragment variable (scFv)/NKG2D-chimeric antigen receptor (CAR) T cells, and explored whether FLT3 inhibitors combined with FLT3scFv/NKG2D-CAR T cells could have synergistic anti-leukaemia effects.

methodsFLT3scFv and NKG2D expression in CAR T cells, FLT3 and NKG2DL expression in AML cells, and the in vitro cytotoxicity of combining CAR T cells with gilteritinib were assessed by flow cytometry. The therapeutic effect was evaluated in a xenograft mouse model established by injection of MOLM-13 cells. Mechanisms underlying the gilteritinib-induced NKG2DL upregulation were investigated using siRNA, ChIP-QPCR and luciferase assays.

resultsThe FLT3scFv/NKG2D-CAR T cells specifically lysed AML cells both in vitro and in the xenograft mouse model. The efficacy of FLT3scFv/NKG2D-CAR T cells was improved by gilteritinib-pretreatment. The noncanonical NF-κB2/Rel B signalling pathway was found to mediate gilteritinib-induced NKG2DL upregulation in AML cells.

conclusionsBispecific FLT3scFv/NKG2D-CAR T cells can effectively eradicate AML cells. The FLT3 inhibitor gilteritinib can synergistically improve this effect by upregulating NF-κB2-dependent NKG2DL expression in AML cells.

Indexed as

Leukemia, Myeloid, AcuteNK Cell Lectin-Like Receptor Subfamily KAniline CompoundsAnimalsDisease Models, Animalfms-Like Tyrosine Kinase 3HumansMiceMutationNF-kappa B p52 SubunitProtein Kinase InhibitorsPyrazinesT-LymphocytesAniline CompoundsFLT3 protein, humanfms-Like Tyrosine Kinase 3gilteritinibNF-kappa B p52 SubunitNK Cell Lectin-Like Receptor Subfamily KProtein Kinase InhibitorsPyrazinesAcute myeloid leukaemiaChimeric antigen receptor (CAR)FLT3 inhibitorFMS-like tyrosine kinase 3 (FLT3)GilteritinibImmunotherapyNatural killer group 2 member D (NKG2D)

Identifiers

PMID35246156
PMCPMC8896098
OpenAlexW4214808386

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.