Evidence map›Paper›PMID 34214199›Full record

ArticleEuropean journal of haematology2021

MCIR1: A patient-derived mantle cell lymphoma line for discovering new treatments for ibrutinib resistance.

Xiaosheng Wu, Kevin E Nowakowski, Jithma P Abeykoon, Michelle Manske, Mary J Stenson, Michael M Timm, Curtis A Hanson, Daniel L Van Dyke, Surendra Dasari, Thomas E Witzig

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

Article in European journal of haematology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.1field-weighted citation impact, top 52% 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

1 citing paper in PubMed, 2 citations in OpenAlex.

  1. Article
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

10 authors at 2 institutions in 1 country.

Xiaosheng WuDivision of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA.ORCID https://orcid.org/0000-0001-8043-2177
Kevin E NowakowskiDivision of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA.
Jithma P AbeykoonDivision of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA.
Michelle ManskeDivision of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA.
Mary J StensonDivision of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA.
Michael M TimmDepartment of Pathology and Laboratory Medicine, Mayo Clinic, Rochester, MN, USA.
Curtis A HansonDepartment of Pathology and Laboratory Medicine, Mayo Clinic, Rochester, MN, USA.
Daniel L Van DykeDepartment of Pathology and Laboratory Medicine, Mayo Clinic, Rochester, MN, USA.
Surendra DasariDepartment of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
Thomas E WitzigDivision of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA.
Mayo Clinic in Arizona · USMayo Clinic in Florida · US

Funding

The Role of Monocytes in non-Hodgkin LymphomaP50CA097274 · NCI · UNIVERSITY OF IOWA · PI LENTZ, STEVEN R · 2002 to 2021
$45.7M
Signal transduction inhibitor therapy for LymphomaR01CA127433 · NCI · MAYO CLINIC ROCHESTER · PI WITZIG, THOMAS E. · 2007 to 2011
$1.7M
NCI NIH HHS CA97274NCI NIH HHS P50 CA097274NCI NIH HHS R01 CA127433Predolin Foundation Biobank
6 · The paper itself

Abstract

backgroundDespite the unprecedented success of ibrutinib in lymphoma therapy, the development of ibrutinib resistance due to acquired BTK or PLCγ2 mutations has become a new clinical problem. However, not all resistance is mediated by these mutations and these mechanisms are poorly understood due to a lack of study tools that truly recapitulate this clinical scenario.

methodsWe established a novel patient-derived ibrutinib-resistant mantle cell lymphoma (MCL) line named MCIR1. Using immunological, molecular, and cytogenetic approaches, we comprehensively characterized MCIR1 and further demonstrated its utility in the study of resistance mechanisms and treatments to overcome this resistance.

resultsWe show that MCIR1 is a bona fide ibrutinib-resistant MCL cell line with normal BTK-/PLCγ2 but ibrutinib-resistant ERK1/2 and AKT1 signaling. RNA-Seq analysis revealed a robust non-canonical NF-kB signaling that drives the ibrutinib resistance. We also demonstrate the potential utility of a MCIR1-based cell and mouse model for the discovery of new treatments to overcome BTK inhibitor resistance.

conclusionsWe have established the first patient-derived ibrutinib-resistant MCL cell line MCIR1 that lacks BTK or PLCγ2 mutations but exhibits a hyperactive non-canonical NF-kB pathway. We further demonstrate its utility in the discovery and validation of new drugs to overcome this resistance.

Indexed as

Founder EffectAdenineAgammaglobulinaemia Tyrosine KinaseAntineoplastic AgentsB-LymphocytesCell Line, TumorDrug Resistance, NeoplasmGene Expression ProfilingGene Expression Regulation, NeoplasticHumansLymphoma, Mantle-CellMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Models, BiologicalNF-kappa BPhospholipase C gammaAdenineAgammaglobulinaemia Tyrosine KinaseAKT1 protein, humanAntineoplastic AgentsBTK protein, humanibrutinibMAPK1 protein, humanMAPK3 protein, humanMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3NF-kappa BPhospholipase C gammaPiperidinesPLCG2 protein, humanProtein Kinase InhibitorsProto-Oncogene Proteins c-aktBTK inhibitorscell lineIbrutinib resistancemantle cell lymphomanon-canonical NF-kB

Identifiers

PMID34214199
PMCPMC8654320
OpenAlexW3176365138

What OpenQuestion holds

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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.