Evidence map›Paper›PMID 29259203›Full record

Trial reportNature communications2017

The evolutionary landscape of chronic lymphocytic leukemia treated with ibrutinib targeted therapy.

Dan A Landau, Clare Sun, Daniel Rosebrock, Sarah E M Herman, Joshua Fein, Mariela Sivina, Chingiz Underbayev, Delong Liu, Julia Hoellenriegel, Sarangan Ravichandran and 12 more

Open access · goldAbstract readClinical Trial, Phase IIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers.

0numbers the graph read from it
0cells of the map it votes in
120citing papers in PubMed
12.0field-weighted citation impact, top 1% 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

120 citing papers in PubMed, 175 citations in OpenAlex.

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  5. Adding Umbralisib and Ublituximab (U2) to Ibrutinib in Patients with CLL: A Phase II Study of an MRD-Driven Approach.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022
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60 more citing papers are in PubMed but not listed here.

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

22 authors at 8 institutions in 2 countries.

Dan A LandauNew York Genome Center, New York, NY, 10013, USA.
Clare SunHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, 20892, USA.ORCID http://orcid.org/0000-0001-8498-4729
Daniel RosebrockBroad Institute, Cambridge, MA, 02142, USA.
Sarah E M HermanHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Joshua FeinNew York Genome Center, New York, NY, 10013, USA.
Mariela SivinaDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Chingiz UnderbayevHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Delong LiuHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Julia HoellenriegelDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Sarangan RavichandranAdvanced Biomedical Computing Center, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc, Frederick, MD, 21701, USA.
Mohammed Z H FarooquiHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Wandi ZhangDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
Carrie CibulskisBroad Institute, Cambridge, MA, 02142, USA.
Asaf ZviranNew York Genome Center, New York, NY, 10013, USA.
Donna S NeubergDepartment of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.ORCID http://orcid.org/0000-0003-2566-3145
Dimitri LivitzBroad Institute, Cambridge, MA, 02142, USA.ORCID http://orcid.org/0000-0003-2528-1446
Ivana BozicDepartment of Applied Mathematics, University of Washington, Seattle, WA, 98195, USA.
Ignaty LeshchinerBroad Institute, Cambridge, MA, 02142, USA.ORCID http://orcid.org/0000-0001-8942-9265
Gad GetzBroad Institute, Cambridge, MA, 02142, USA.ORCID http://orcid.org/0000-0002-0936-0753
Jan A BurgerDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Adrian WiestnerHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, 20892, USA. wiestnea@nhlbi.nih.gov.
Catherine J WuBroad Institute, Cambridge, MA, 02142, USA. cwu@partners.org.
Broad Institute · USNational Institutes of Health · USThe University of Texas MD Anderson Cancer Center · USDana-Farber Cancer Institute · USCornell University · USLeidos (United States) · USTel Aviv University · ILUniversity of Washington Applied Physics Laboratory · US

Funding

Large Scale Sequencing and Analysis of GenomesU54HG003067 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GABRIEL, STACEY, LANDER, ERIC S · 2004 to 2015
$568.6M
Tumor microenvironment in CLL and MCL: pathogenesis, targets, and therapyZIAHL002346 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI WIESTNER, ADRIAN U · 2009 to 2025
$29.8M
ProteomicsP01CA206978 · NCI · DANA-FARBER CANCER INST · PI GETZ, GAD A · 2016 to 2025
$17.0M
(PQ8) Genetically faithful murine models for studying disease progression in chronic lymphocytic leukemiaR01CA216273 · NCI · DANA-FARBER CANCER INST · PI WANG, LILI, WU, CATHERINE JU-YING · 2017 to 2021
$3.5M
ITSC for Leukemia: Novel Molecular Strategies for NCTN: "Individualized" TherapieU10CA180861 · NCI · OHIO STATE UNIVERSITY · PI BLOOMFIELD, CLARA D, MARCUCCI, GUIDO · 2014 to 2018
$3.4M
Statistical methods for analysis of single-cell variabilityR01HL131768 · NHLBI · HARVARD MEDICAL SCHOOL · PI KHARCHENKO, PETER V · 2015 to 2019
$2.4M
(PQD1) lmpact of cytotoxic and targeted therapy on clonal evolution of CLLR01CA184922 · NCI · DANA-FARBER CANCER INST · PI WU, CATHERINE JU-YING · 2014 to 2017
$2.2M
The role of the SF3B1 splicing factor in chronic lymphocytic leukemiaR01HL116452 · NHLBI · DANA-FARBER CANCER INST · PI WU, CATHERINE JU-YING · 2013 to 2017
$2.1M
Defining the impact of clonal evolution on chronic lymphocytic leukemiaR01CA182461 · NCI · DANA-FARBER CANCER INST · PI WU, CATHERINE JU-YING · 2014 to 2018
$1.8M
The role of epigenetic heterogeneity in CLL evolution Admin supplementK01ES025431 · NIEHS · WEILL MEDICAL COLL OF CORNELL UNIV · PI LANDAU, DAN · 2014 to 2018
$982k
NCI NIH HHS P01 CA206978NCI NIH HHS R01 CA182461NCI NIH HHS R01 CA184922NCI NIH HHS R01 CA216273NCI NIH HHS U10 CA180861NHGRI NIH HHS U54 HG003067NHLBI NIH HHS R01 HL116452NHLBI NIH HHS R01 HL131768NIEHS NIH HHS K01 ES025431
6 · The paper itself

Abstract

Treatment of chronic lymphocytic leukemia (CLL) has shifted from chemo-immunotherapy to targeted agents. To define the evolutionary dynamics induced by targeted therapy in CLL, we perform serial exome and transcriptome sequencing for 61 ibrutinib-treated CLLs. Here, we report clonal shifts (change >0.1 in clonal cancer cell fraction, Q < 0.1) in 31% of patients during the first year of therapy, associated with adverse outcome. We also observe transcriptional downregulation of pathways mediating energy metabolism, cell cycle, and B cell receptor signaling. Known and previously undescribed mutations in BTK and PLCG2, or uncommonly, other candidate alterations are present in seventeen subjects at the time of progression. Thus, the frequently observed clonal shifts during the early treatment period and its potential association with adverse outcome may reflect greater evolutionary capacity, heralding the emergence of drug-resistant clones.

Indexed as

AdenineAdultAgammaglobulinaemia Tyrosine KinaseAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsClonal EvolutionDisease ProgressionDown-RegulationDrug Resistance, NeoplasmExome SequencingFemaleGene Expression Regulation, NeoplasticHumansLeukemia, Lymphocytic, Chronic, B-CellLongitudinal StudiesAdenineAgammaglobulinaemia Tyrosine KinaseBTK protein, humanibrutinibPhospholipase C gammaPiperidinesProtein-Tyrosine KinasesPyrazolesPyrimidinesRituximab

Identifiers

PMID29259203
PMCPMC5736707
OpenAlexW2773946416

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Registered trials

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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.