Evidence map›Paper›PMID 35794565›Full record

ArticleJournal of translational medicine2022

Autophagy activation mediates resistance to FLT3 inhibitors in acute myeloid leukemia with FLT3-ITD mutation.

Dan Xu, Yishan Chen, Ying Yang, Zhao Yin, Changfen Huang, Qiang Wang, Ling Jiang, Xuejie Jiang, Changxin Yin, Qifa Liu and 1 more

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

Article in Journal of translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
1.6field-weighted citation impact, top 15% 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, 1 synthesis or guideline pooled it, 10 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Review
  5. Review
  6. Review
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

11 authors at 1 institution in 1 country.

Dan XuDepartment of Hematology, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Avenue North, Guangzhou, 510515, China.
Yishan ChenDepartment of Hematology, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Avenue North, Guangzhou, 510515, China.
Ying YangDepartment of Hematology, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Avenue North, Guangzhou, 510515, China.
Zhao YinDepartment of Hematology, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Avenue North, Guangzhou, 510515, China.
Changfen HuangDepartment of Hematology, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Avenue North, Guangzhou, 510515, China.
Qiang WangDepartment of Hematology, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Avenue North, Guangzhou, 510515, China.
Ling JiangDepartment of Hematology, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Avenue North, Guangzhou, 510515, China.
Xuejie JiangDepartment of Hematology, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Avenue North, Guangzhou, 510515, China.
Changxin YinDepartment of Hematology, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Avenue North, Guangzhou, 510515, China.
Qifa LiuDepartment of Hematology, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Avenue North, Guangzhou, 510515, China.
Guopan YuDepartment of Hematology, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Avenue North, Guangzhou, 510515, China. yugpp@163.com.ORCID 0000-0002-5732-0318
Nanfang Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAutophagy plays a critical role in drug resistance in acute myeloid leukemia (AML), including the subtype with FLT3-ITD mutation. Yet how autophagy is activated and mediates resistance to FLT3 inhibitors in FLT3-ITD-positive AML remains unsure.

methodsWe detected the expression of autophagy markers in FLT3-ITD-positive leukemic cells after vs. before acquired resistance to FLT3 inhibitors; tested the stimulative effect of acquired D835Y mutation and bone marrow micro-environment (BME) on autophagy; explored the mechanism of autophagy mediating FLT3 inhibitor resistance.

resultsSorafenib-resistant cells markedly overpresented autophagy markers in comparison with sorafenib-sensitive cells or the cells before sorafenib treatment. Both acquired D835Y mutation and BME activated cytoprotective autophagy to mediate FLT3 inhibitor resistance. Autophagy activation decreased the suppression efficacy of FLT3 inhibitors on FLT3 downstream signaling and then weakened their anti-leukemia effect. Inhibition of autophagy with CQ significantly enhanced the suppressive effect of FLT3 inhibitor on FLT3 downstream signaling, in the end overcame resistance to FLT3 inhibitors.

conclusionsAutophagy might be stimulated by acquired mutation or BME, and bypass activate FLT3 downstream signaling to mediate FLT3 inhibitor resistance in FLT3-ITD-positive AML. Targeting autophagy could be a promising strategy to overcome resistance.

Indexed as

Drug Resistance, NeoplasmLeukemia, Myeloid, AcuteAutophagyfms-Like Tyrosine Kinase 3HumansMutationProtein Kinase InhibitorsSorafenibTumor MicroenvironmentFLT3 protein, humanfms-Like Tyrosine Kinase 3Protein Kinase InhibitorsSorafenibAcquired mutationAcute myeloid leukemiaAutophagyBone marrow micro-environmentFLT3 inhibitorFLT3-ITDResistance

Identifiers

PMID35794565
PMCPMC9258138
OpenAlexW4283829861

What OpenQuestion holds

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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.