Evidence map›Paper›PMID 31801949›Full record

ArticleCell death & disease2019

Resistance to BTK inhibition by ibrutinib can be overcome by preventing FOXO3a nuclear export and PI3K/AKT activation in B-cell lymphoid malignancies.

Isha Kapoor, Yue Li, Arishya Sharma, Huayuan Zhu, Juraj Bodo, Wei Xu, Eric D Hsi, Brian T Hill, Alexandru Almasan

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

Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed, 2 pooled it
5.7field-weighted citation impact, top 3% 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

57 citing papers in PubMed, 2 syntheses or guidelines pooled it, 76 citations in OpenAlex.

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  12. [Mechanism of BIM-induced ibrutinib resistance in chronic lymphocytic leukemia].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2025
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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

9 authors at 3 institutions in 2 countries.

Isha KapoorDepartment of Cancer Biology, Lerner Research Institute, Cleveland, OH, USA.
Yue LiDepartment of Hematology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Arishya SharmaDepartment of Cancer Biology, Lerner Research Institute, Cleveland, OH, USA.
Huayuan ZhuDepartment of Hematology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Juraj BodoDepartment of Laboratory Medicine, Institute of Pathology and Laboratory Medicine, Cleveland, OH, USA.
Wei XuDepartment of Hematology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Eric D HsiDepartment of Laboratory Medicine, Institute of Pathology and Laboratory Medicine, Cleveland, OH, USA.
Brian T HillDepartment of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland, OH, USA.
Alexandru AlmasanDepartment of Cancer Biology, Lerner Research Institute, Cleveland, OH, USA. almasaa@ccf.org.ORCID http://orcid.org/0000-0002-8916-6650
Jiangsu Province Hospital · CNCleveland Clinic Lerner College of Medicine · USCleveland Clinic · US

Funding

Therapeutic resistance in leukemic cells: targeting BCL-2 family and autophagyR01CA184137 · NCI · CLEVELAND CLINIC LERNER COM-CWRU · PI ALMASAN, ALEXANDRU · 2015 to 2019
$1.8M
NCI NIH HHS R01 CA184137U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) CA184137
6 · The paper itself

Abstract

Chronic activation of the Bruton's tyrosine kinase (BTK)-mediated B-cell receptor (BCR) signaling is a hallmark of many B-cell lymphoid malignancies, including chronic lymphocytic leukemia (CLL) and diffuse large B-cell lymphoma (DLBCL). Ibrutinib, an FDA approved, orally administered BTK inhibitor, has demonstrated high response rates, however, complete responses are infrequent and acquired resistance to BTK inhibition can emerge. In this study, we generated ibrutinib-resistant (IB-R) cell lines by chronic exposure of CLL and activated B-cell (ABC)-DLBCL cells to ibrutinib in order to investigate the mechanism of acquired resistance to ibrutinib. IB-R cell lines demonstrated downregulation of FOXO3a and PTEN levels and activation of AKT, with their levels being low in the nuclei of resistant cells in comparison to the sensitive counterparts. Inhibition of PI3K and AKT using idelalisib and MK2206, respectively increased ibrutinib-induced apoptosis in IB-R cells by downregulation of pAKT

Indexed as

Agammaglobulinaemia Tyrosine KinaseAgedApoptosisCell Line, TumorCell ProliferationDrug Resistance, NeoplasmForkhead Box Protein O3HumansLeukemia, Lymphocytic, Chronic, B-CellLymphoma, Large B-Cell, DiffuseMaleMiddle AgedPhosphatidylinositol 3-KinasesProtein Kinase InhibitorsProto-Oncogene Proteins c-aktPTEN PhosphohydrolaseAgammaglobulinaemia Tyrosine KinaseForkhead Box Protein O3FOXO3 protein, humanidelalisibPhosphatidylinositol 3-KinasesProtein Kinase InhibitorsProto-Oncogene Proteins c-aktPTEN PhosphohydrolasePTEN protein, humanPurinesQuinazolinones

Identifiers

PMID31801949
PMCPMC6892912
OpenAlexW2993793724

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.