Evidence map›Paper›PMID 35421218›Full record

ArticleBlood2022

CD34+CD19-CD22+ B-cell progenitors may underlie phenotypic escape in patients treated with CD19-directed therapies.

Clara Bueno, Susana Barrera, Alex Bataller, Valentín Ortiz-Maldonado, Natalina Elliot, Sorcha O'Byrne, Guanlin Wang, Montse Rovira, Francisco Gutierrez-Agüera, Juan L Trincado and 21 more

Open access · hybridAbstract read
In one paragraph

Article in Blood, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
3.5field-weighted citation impact, top 6% 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

25 citing papers in PubMed, 34 citations in OpenAlex.

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  19. Circulating IRF8-expressing CD123Trends in immunology · 2023
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

31 authors at 10 institutions in 2 countries.

Clara BuenoJosep Carreras Leukemia Research Institute, Campus Clinic, Barcelona, Spain.ORCID 0000-0003-1442-6216
Susana BarreraCentro de Investigación Biomédica en Red en Oncología (CIBER-ONC) and.
Alex BatallerJosep Carreras Leukemia Research Institute, Campus Clinic, Barcelona, Spain.ORCID 0000-0002-6085-2745
Valentín Ortiz-MaldonadoDepartment of Clinical Hematology, Hospital Clinic of Barcelona, Barcelona, Spain.ORCID 0000-0003-4699-6862
Natalina ElliotDepartment of Paediatrics, Children's Hospital, John Radcliffe Hospital.
Sorcha O'ByrneDepartment of Paediatrics, Children's Hospital, John Radcliffe Hospital.ORCID 0000-0002-3116-1646
Guanlin WangMRC (Medical Research Council) Molecular Haematology Unit, and.
Montse RoviraCentre for Computational Biology, MRC Weatherall Institute of Molecular Medicine (WIMM), University of Oxford, Oxford, United Kingdom.
Francisco Gutierrez-AgüeraJosep Carreras Leukemia Research Institute, Campus Clinic, Barcelona, Spain.
Juan L TrincadoJosep Carreras Leukemia Research Institute, Campus Clinic, Barcelona, Spain.ORCID 0000-0001-5363-3774
María González-GonzálezCentro de Investigación Biomédica en Red en Oncología (CIBER-ONC) and.ORCID 0000-0001-8115-1086
Mireia MorgadesClinical Hematology Department, ICO-Hospital Germans Trias i Pujol, Badalona, Spain.ORCID 0000-0003-0295-2534
Marc SoriguéClinical Hematology Department, ICO-Hospital Germans Trias i Pujol, Badalona, Spain.ORCID 0000-0002-0587-591X
Paloma BárcenaCentro de Investigación Biomédica en Red en Oncología (CIBER-ONC) and.
Samanta Romina ZanettiJosep Carreras Leukemia Research Institute, Campus Clinic, Barcelona, Spain.ORCID 0000-0002-9052-8751
Montse TorrebadellHaematology Laboratory, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain.ORCID 0000-0002-0027-3215
Nerea Vega-GarciaHaematology Laboratory, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain.ORCID 0000-0002-3190-063X
Susana RivesCentro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, Madrid, Spain.ORCID 0000-0002-5658-1831
Mar MalloJosep Carreras Leukaemia Research Institute (IJC), Campus ICO-Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona (UAB), Badalona, Spain.ORCID 0000-0001-7741-498X
Francesc SoleJosep Carreras Leukaemia Research Institute (IJC), Campus ICO-Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona (UAB), Badalona, Spain.ORCID 0000-0002-3251-2161
Adam J MeadDepartment of Paediatrics, Children's Hospital, John Radcliffe Hospital.ORCID 0000-0001-8522-1002
Irene RobertsDepartment of Paediatrics, Children's Hospital, John Radcliffe Hospital.
Supat ThongjueaDepartment of Paediatrics, Children's Hospital, John Radcliffe Hospital.ORCID 0000-0002-9129-4694
Bethan PsailaDepartment of Paediatrics, Children's Hospital, John Radcliffe Hospital.ORCID 0000-0001-8198-9663
Manel JuanRed Española de Terapias Avanzadas (TERAV), Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS RD21/0017/0029), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.ORCID 0000-0002-3064-1648
Julio DelgadoCentro de Investigación Biomédica en Red en Oncología (CIBER-ONC) and.ORCID 0000-0002-5157-4376
Alvaro Urbano-IspizúaJosep Carreras Leukemia Research Institute, Campus Clinic, Barcelona, Spain.
Josep María RiberaRed Española de Terapias Avanzadas (TERAV), Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS RD21/0017/0029), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.ORCID 0000-0003-1042-6024
Alberto OrfaoCentro de Investigación Biomédica en Red en Oncología (CIBER-ONC) and.
Anindita RoyDepartment of Paediatrics, Children's Hospital, John Radcliffe Hospital.
Pablo MenendezJosep Carreras Leukemia Research Institute, Campus Clinic, Barcelona, Spain.
Instituto de Salud Carlos III · ESJohn Radcliffe Hospital · GBHospital Sant Joan de Déu Barcelona · ESUniversidad de Salamanca · ESUniversitat Autònoma de Barcelona · ESJosep Carreras Leukaemia Research Institute · ESUniversity of Oxford · GBHospital Clínic de Barcelona · ESHospital Universitari Germans Trias i Pujol · ESInstitució Catalana de Recerca i Estudis Avançats · ES

Funding

Cancer Research UK 26988Cancer Research UK 27125Cancer Research UK 27723Cancer Research UK 28051Cancer Research UK 29034Medical Research Council G84/6443Medical Research Council MC_UU_00016/15Medical Research Council MC_UU_00029/7Medical Research Council MC_UU_12009/14Medical Research Council MC_UU_12009/16Medical Research Council MR/L006340/1Medical Research Council MR/M00919X/1Medical Research Council MR/R006237/1Wellcome Trust
6 · The paper itself

Abstract

CD19-directed immunotherapies have revolutionized the treatment of advanced B-cell acute lymphoblastic leukemia (B-ALL). Despite initial impressive rates of complete remission (CR) many patients ultimately relapse. Patients with B-ALL successfully treated with CD19-directed T cells eventually relapse, which, coupled with the early onset of CD22 expression during B-cell development, suggests that preexisting CD34+CD22+CD19- (pre)-leukemic cells represent an "early progenitor origin-related" mechanism underlying phenotypic escape to CD19-directed immunotherapies. We demonstrate that CD22 expression precedes CD19 expression during B-cell development. CD34+CD19-CD22+ cells are found in diagnostic and relapsed bone marrow samples of ∼70% of patients with B-ALL, and their frequency increases twofold in patients with B-ALL in CR after CD19 CAR T-cell therapy. The median of CD34+CD19-CD22+ cells before treatment was threefold higher in patients in whom B-ALL relapsed after CD19-directed immunotherapy (median follow-up, 24 months). Fluorescence in situ hybridization analysis in flow-sorted cell populations and xenograft modeling revealed that CD34+CD19-CD22+ cells harbor the genetic abnormalities present at diagnosis and initiate leukemogenesis in vivo. Our data suggest that preleukemic CD34+CD19-CD22+ progenitors underlie phenotypic escape after CD19-directed immunotherapies and reinforce ongoing clinical studies aimed at CD19/CD22 dual targeting as a strategy for reducing CD19- relapses. The implementation of CD34/CD19/CD22 immunophenotyping in clinical laboratories for initial diagnosis and subsequent monitoring of patients with B-ALL during CD19-targeted therapy is encouraged.

Indexed as

Antigens, CD19Burkitt LymphomaAntigens, CD34B-LymphocytesHumansImmunophenotypingIn Situ Hybridization, FluorescenceRecurrenceSialic Acid Binding Ig-like Lectin 2Antigens, CD19Antigens, CD34CD22 protein, humanSialic Acid Binding Ig-like Lectin 2

Identifiers

PMID35421218
PMCPMC9346957
OpenAlexW4223906335

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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.