The immune checkpoint ICOSLG is a relapse-predicting biomarker and therapeutic target in infant t(4;11) acute lymphoblastic leukemia

Külp, Marius; Siemund, Anna Lena; Larghero, Patrizia; Dietz, Alissa; Alten, Julia; Cario, Gunnar; Eckert, Cornelia; Caye-Eude, Aurélie; Cavé, Hélène; Bardini, Michela; Cazzaniga, Giovanni; Lorenzo, Paola De; Valsecchi, Maria Grazia; Diehl, Laura; Bonig, Halvard; Meyer, Claus; Marschalek, Rolf

doi:10.1016/j.isci.2022.104613

Cited by 6 publications

(12 citation statements)

References 82 publications

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“…CD25 + FOXP3 + Tregs were gated and their percentage among the CD4 + population was quantified. Figure taken from Külp et al. (2022) .…”

Section: Step-by-step Methods Detailsmentioning

confidence: 99%

“…The t(4;11) acute lymphoblastic leukemia (ALL) cell line SEM was stably transfected with the open reading frame (ORF) of the EGR3 gene (SEM::EGR3) which has been identified as a transactivator of ICOSLG ( Külp et al., 2022 ). The empty vector transfected cell line SEM::mock served as a control.…”

Section: Before You Beginmentioning

confidence: 99%

“…Error bars represent the standard error of mean of HD1, HD2, and HD3. Figures taken from Külp et al. (2022) .…”

Section: Expected Outcomesmentioning

confidence: 99%

“…The protocol is applicable for MHC-matched and -unmatched experiments and allows assessment of Treg expansion without using a mouse model. For complete details on the use and execution of this protocol, please refer to Külp et al. (2022) .…”

mentioning

confidence: 99%

“…For complete details on the use and execution of this protocol, please refer to Külp et al. (2022) .…”

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confidence: 99%

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Co-culture of primary human T cells with leukemia cells to measure regulatory T cell expansion

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“…CD25 + FOXP3 + Tregs were gated and their percentage among the CD4 + population was quantified. Figure taken from Külp et al. (2022) .…”

Section: Step-by-step Methods Detailsmentioning

confidence: 99%

Section: Before You Beginmentioning

confidence: 99%

“…Error bars represent the standard error of mean of HD1, HD2, and HD3. Figures taken from Külp et al. (2022) .…”

Section: Expected Outcomesmentioning

confidence: 99%

mentioning

confidence: 99%

“…For complete details on the use and execution of this protocol, please refer to Külp et al. (2022) .…”

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confidence: 99%

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Co-culture of primary human T cells with leukemia cells to measure regulatory T cell expansion

et al. 2022

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The EGR3 regulome of infant KMT2A-r acute lymphoblastic leukemia identifies differential expression of B-lineage genes predictive for outcome

Külp

Larghero

Alten³

et al. 2023

Leukemia

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KMT2A-rearranged acute lymphoblastic infant leukemia (KMT2A-r iALL) is associated with outsize risk of relapse and relapse mortality. We previously reported strong upregulation of the immediate early gene EGR3 in KMT2A::AFF1 iALL at relapse; now we provide analyses of the EGR3 regulome, which we assessed through binding and expression target analysis of an EGR3-overexpressing t(4;11) cell culture model. Our data identify EGR3 as a regulator of early B-lineage commitment. Principal component analysis of 50 KMT2A-r iALL patients at diagnosis and 18 at relapse provided strictly dichotomous separation of patients based on the expression of four B-lineage genes. Absence of B-lineage gene expression translates to more than two-fold poorer long-term event-free survival. In conclusion, our study presents four B-lineage genes with prognostic significance, suitable for gene expression-based risk stratification of KMT2A-r iALL patients.

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A human genome editing–based MLL::AF4 ALL model recapitulates key cellular and molecular leukemogenic features

Bueno,

Torres-Ruiz,

Velasco-Hernandez

et al. 2023

Blood

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The immune checkpoint ICOSLG is a relapse-predicting biomarker and therapeutic target in infant t(4;11) acute lymphoblastic leukemia

Cited by 6 publications

References 82 publications

Co-culture of primary human T cells with leukemia cells to measure regulatory T cell expansion

Co-culture of primary human T cells with leukemia cells to measure regulatory T cell expansion

The EGR3 regulome of infant KMT2A-r acute lymphoblastic leukemia identifies differential expression of B-lineage genes predictive for outcome

A human genome editing–based MLL::AF4 ALL model recapitulates key cellular and molecular leukemogenic features

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