Evidence map›Paper›PMID 27904766›Full record

ArticleAmerican journal of cancer research2016

The role of PIM1 in the ibrutinib-resistant ABC subtype of diffuse large B-cell lymphoma.

Hsu-Ping Kuo, Scott A Ezell, Sidney Hsieh, Karl J Schweighofer, Leo Wk Cheung, Shiquan Wu, Mutiah Apatira, Mint Sirisawad, Karl Eckert, Yu Liang and 4 more

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

Article in American journal of cancer research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed, 1 pooled it
4.4field-weighted citation impact, top 5% 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

43 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.

  1. Pooled it
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  7. Article
  8. Audit of B-cell cancer genes.Blood advances · 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

14 authors at 1 institution in 1 country.

Hsu-Ping KuoDepartment of Research, Pharmacyclics, LLC, an AbbVie Company Sunnyvale, CA, USA.
Scott A EzellDepartment of Research, Pharmacyclics, LLC, an AbbVie Company Sunnyvale, CA, USA.
Sidney HsiehDepartment of Research, Pharmacyclics, LLC, an AbbVie Company Sunnyvale, CA, USA.
Karl J SchweighoferDepartment of Research, Pharmacyclics, LLC, an AbbVie Company Sunnyvale, CA, USA.
Leo Wk CheungDepartment of Research, Pharmacyclics, LLC, an AbbVie Company Sunnyvale, CA, USA.
Shiquan WuDepartment of Research, Pharmacyclics, LLC, an AbbVie Company Sunnyvale, CA, USA.
Mutiah ApatiraDepartment of Research, Pharmacyclics, LLC, an AbbVie Company Sunnyvale, CA, USA.
Mint SirisawadDepartment of Research, Pharmacyclics, LLC, an AbbVie Company Sunnyvale, CA, USA.
Karl EckertDepartment of Research, Pharmacyclics, LLC, an AbbVie Company Sunnyvale, CA, USA.
Yu LiangDepartment of Research, Pharmacyclics, LLC, an AbbVie Company Sunnyvale, CA, USA.
Jeff HsuDepartment of Research, Pharmacyclics, LLC, an AbbVie Company Sunnyvale, CA, USA.
Chun-Te ChenDepartment of Research, Pharmacyclics, LLC, an AbbVie Company Sunnyvale, CA, USA.
Darrin BeaupreDepartment of Research, Pharmacyclics, LLC, an AbbVie Company Sunnyvale, CA, USA.
Betty Y ChangDepartment of Research, Pharmacyclics, LLC, an AbbVie Company Sunnyvale, CA, USA.
Pharmacyclics (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Diffuse large B cell lymphoma (DLBCL) is a heterogeneous lymphoma and the most common subtype of non-Hodgkin lymphoma, accounting for roughly 30% of newly diagnosed cases in the United States. DLBCL can be separated into the activated B cell-like (ABC) and germinal center B cell-like (GCB) subtypes, with distinct gene expression profiles, oncogenic aberrations, and clinical outcomes. ABC-DLBCL is characterized by chronically active B-cell receptor (BCR) signaling that can be modulated by Bruton's tyrosine kinase (BTK) activity. Thus, BTK serves as an attractive therapeutic target in this type of B-cell malignancy. Ibrutinib, a first-in-class, orally available covalent BTK inhibitor, has demonstrated clinical activity in several B-cell leukemias and lymphomas. A phase 1/2 clinical trial of single-agent ibrutinib in relapsed and refractory DLBCL patients revealed an overall response rate of 37% in ABC-DLBCL patients. However, responses to kinase-directed therapies are often limited by emerging resistance mechanisms that bypass the therapeutic target. Here we report the discovery of point mutations within the kinase PIM1 that reduce sensitivity to ibrutinib in ABC-DLBCL. These mutations stabilize PIM1 and affect upstream regulators and downstream targets of NF-κB signaling. The introduction of mutant PIM1 into an ABC-DLBCL cell line, TMD8, increased colony formation and decreased sensitivity to ibrutinib. In addition, ibrutinib-resistant cell lines generated by prolonged ibrutinib exposure

Indexed as

Bruton’s tyrosine kinaseDLBCLibrutinibPIM1

Identifiers

PMID27904766
PMCPMC5126268
OpenAlexW2560507939

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.