PXD058992

PXD058992 is an original dataset announced via ProteomeXchange.

Title	Optimized Method for Cell Surface Protein Identification on Primary B-Cell Precursor Acute Lymphoblastic Leukemia Cells
Description	B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is caused by abnormal expansion of immature B cells. Genetic alterations can be identified in most of the BCP-ALL cases, however, some specific lesions including rearrangements of the mixed lineage leukemia (MLL) gene encoding lysine methyltransferase 2A (KMT2A) are associated with particularly poor prognosis. This MLL-rearranged subtype of leukemia poorly responds to conventional treatment and frequently undergoes a lymphoid-to-myeloid lineage switch in response to CD19-directed immunotherapy with consequent loss of B cell-specific targets for immunotherapy. Therefore, there is an urgent need to identify new targets for treatment of relapsed/refractory MLLr-BCP-ALL. Attractive targets may be found in a cell surfaceome, as membrane proteins are often expressed abnormally on cancer cells and are more accessible for therapeutics. Membrane proteins also play key roles in mediating external signaling and interactions with the microenvironment, thus being essential for cancer cell survival. RNA-based data may not always correlate with plasma membrane protein levels. Therefore, we performed the analysis of the BCP-ALL cell surfaceome by biotin labeling of plasma membrane proteins followed by tandem mass spectrometry (LC-MS/MS). This method requires high cell input and therefore was previously applied mainly to cell lines. However, the cell lines often do not fully represent primary samples due to genetic modifications and culture conditions. We have optimized the protocol of plasma membrane protein isolation and LC-MS/MS identification of patient-derived xenografts (PDXs) BCP-ALL cells. We confirmed the LC-MS/MS results by flow cytometry. Additionally, we compared the surfaceomes of PDXs BCP-ALL cells with BCP-ALL cell lines. We profiled six BCP-ALL PDXs and one cell line SEM, all with MLL translocations. In BCP-ALL PDXs we identified 1409 membrane-associated proteins, 945 of which were present in at least 3 samples. Tissue specificity analysis demonstrated that 93 of these proteins are specific for lymphoid cells, including already reported promising immunotherapeutic targets CD19, CD22, CD38, CD70, CD72, CD79A, and CD79B. The expression of selected proteins was confirmed by flow cytometry and compared to the expression on B-ALL cell lines with MLL translocation. Moreover, we identified an additional subset of proteins with potential therapeutic significance, including CD48, IL7R, ITGB7, LAIR1, LILRB1. Importantly, we observed profound differences between surfaceomes of BCP-ALL cell lines and PDX cells.
HostingRepository	PRIDE
AnnounceDate	2025-06-09
AnnouncementXML	Submission_2025-06-08_16:21:02.671.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD058992
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Agata Malinowska
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	methylthiolated residue; monohydroxylated residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-12-18 07:17:46	ID requested
⏵ 1	2025-06-08 16:21:03	announced

10.1038/s41375-025-02580-z;

10.6019/PXD058992;

Marhelava K, Fidyt K, Pepek M, Krawczyk M, Forcados C, Malinowska A, Swiderska B, Fernandez-Fuentes N, Czerwik N, Baranowska I, Krzywdzinska A, Sedek L, Slota L, Perkowski B, Villatoro A, Leray T, Lech-Maranda E, Menendez P, Inderberg EM, W, ä, lchli S, Winiarska M, Firczuk M, LILRB1-directed CAR-T cells for the treatment of hematological malignancies. Leukemia, 39(6):1395-1411(2025) [pubmed]

submitter keyword: leukemia, patient-derived xenograft, mixed lineage leukemia, target, B cell, immunotherapy, PDX, biotinylation,BCP-ALL, surfaceome

Malgorzata Firczuk
contact affiliation	Immunology Department, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland
contact email	mfirczuk@imdik.pan.pl
lab head
Agata Malinowska
contact affiliation	IBB PAS
contact email	esme@ibb.waw.pl
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/06/PXD058992

PRIDE project URI

• PRIDE
  1. PXD058992
     1. Label: PRIDE project
     2. Name: Optimized Method for Cell Surface Protein Identification on Primary B-Cell Precursor Acute Lymphoblastic Leukemia Cells