PXD024112

PXD024112 is an original dataset announced via ProteomeXchange.

Title	Retroviral transduction of NOTCH1 into primary human Chronic Lymphocytic Leukemia cells unravels immune escape-mechanisms
Description	Functional studies to investigate gene mutations recurrent in B cell lymphoma have been hampered by the inability to genetically manipulate primary cells, attributed to low transduction efficacy and procedure-associated toxicity. Alternative approaches utilize cell lines and mouse models, which often only poorly represent the genomic complexity and biology of the primary malignancy. To overcome these limitations, we have developed a method to retrovirally transfer genes into primary malignant B cells with high transduction efficacy and minimal toxicity. Using this method, we investigated the functions of NOTCH1, the most commonly mutated gene in CLL, by generating isogenic primary tumor cells from patients with Chronic Lymphocytic Leukemia (CLL) and Mantle Cell Lymphoma (MCL), differing only in their expression of NOTCH1. Our data demonstrate that NOTCH1 facilitates immune escape of malignant B cells by up-regulating PD-L1, partly dependent on autocrine interferon-g signaling. In addition, NOTCH1 causes silencing of the entire HLA-class II locus via suppression of the transcriptional co-activator CIITA. These NOTCH1-mediated immune escape mechanisms are associated with the expansion of CD4+ T cells in vivo, further contributing to the poor clinical outcome of NOTCH1-mutated CLL and MCL
HostingRepository	PRIDE
AnnounceDate	2022-08-26
AnnouncementXML	Submission_2022-08-26_05:27:31.400.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Valar Nila Roamio Franklin
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; methylthiolated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-02-10 07:19:02	ID requested
⏵ 1	2022-08-26 05:27:31	announced

Dataset with its publication pending

submitter keyword: NOTCH1, Mutated gene, HLA-class II locus, co-activator CIITA, Chronic Lymphocytic Leukemia (CLL), Mantle Cell Lymphoma (MCL)

Clive D'Santos
contact affiliation	Head of the Department, Proteomics Core
contact email	Clivesdsantos@gmail.com
lab head
Valar Nila Roamio Franklin
contact affiliation	Research Assistant
contact email	Valar.Franklin@cruk.cam.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD024112
     1. Label: PRIDE project
     2. Name: Retroviral transduction of NOTCH1 into primary human Chronic Lymphocytic Leukemia cells unravels immune escape-mechanisms