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Discovery of tumor specific antigens in acute myeloid leukemia.

ABSTRACT: Discovery of tumor specific antigens in acute myeloid leukemia.

PROVIDER: PRJNA615163 | ENA |

REPOSITORIES: ENA

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Immune surveillance of acute myeloid leukemia is mediated by HLA-presented antigens on leukemia progenitor cells

Project description:Persistent therapy-resistant leukemic progenitor cells (LPC) are a main cause of disease relapse and recurrence in acute myeloid leukemia (AML). Specific LPC-targeting therapies may thus improve treatment outcome of AML patients. We demonstrate that LPCs present human leukocyte antigen (HLA)-restricted cancer antigens that induce T cell responses allowing for immune surveillance of AML. Using a mass spectrometry-based immunopeptidomics approach we characterized the antigenic landscape of patient LPCs and identify AML/LPC-associated HLA-presented antigens as well as mutation-derived and cryptic neoepitopes as prime targets for development of T cell-based immunotherapeutic approaches. We observed frequent spontaneous memory T cells targeting these AML/LPC-associated antigens in AML patients and showed that antigen-specific T cell recognition and HLA class II immunopeptidome diversity impacts clinical outcome. Our results pave the way for implementation of AML/LPC-associated antigens for T cell-based immunotherapeutic approaches to specifically target and eliminate residual LPCs in AML patients.

2023-08-23 | PXD038691 | Pride

Immune surveillance of acute myeloid leukemia is mediated by HLA-presented antigens on leukemia progenitor cells

Project description:Persistent therapy-resistant leukemia progenitor cells (LPC) are a main cause of disease relapse and recurrence in acute myeloid leukemia (AML). Specific LPC-targeting therapies may thus improve treatment outcome of AML patients. We demonstrated that LPCs present human leukocyte antigen (HLA)-restricted cancer antigens that induce T cell responses allowing for immune surveillance of AML. Using a mass spectrometry-based immunopeptidomics approach, we characterized the antigenic landscape of patient LPCs and identified AML/LPC-associated HLA-presented antigens including mutation-derived and cryptic neoepitopes as prime targets for development of T cell-based immunotherapeutic approaches. We observed frequent spontaneous memory T cells targeting these AML/LPC-associated antigens in AML patients and showed that antigen-specific T cell recognition and HLA class II immunopeptidome diversity impacts clinical outcome. Our results pave the way for implementation of AML/LPC-associated antigens for T cell-based immunotherapeutic approaches to specifically target and eliminate residual LPCs in AML patients.

2023-08-23 | GSE235080 | GEO

Drug-resistant acute myeloid leukemia

Project description:Drug-resistant acute myeloid leukemia

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Proteomic and Phosphoproteomic Landscapes of Acute Myeloid Leukemia

Project description:Label-free quantitation dataset from 44 representative Acute Myeloid Leukemia (AML) patients from the LAML TCGA dataset, and 6 healthy bone marrow derived controls including 3 lineage-depleted and 3 CD34+ selected bone marrows.

2022-03-09 | MSV000089029 | MassIVE

Proteomic and Phosphoproteomic Landscapes of Acute Myeloid Leukemia

Project description:A deep-scale proteome and phosphoproteome database from 44 representative Acute Myeloid Leukemia (AML) patients from the LAML TCGA dataset, and 6 healthy bone marrow derived controls including 3 lineage-depleted and 3 CD34+ selected bone marrows.

2022-03-07 | MSV000089012 | MassIVE

Discovery of tumor specific antigens in acute myeloid leukemia.

Project description:We performed RNA-Seq and mass spectrometry (MS) on the immunopeptidome of 19 human primary AML samples and discovered a set of 58 tumor specific antigens (TSA) that could serve to design an anti-AML immunotherapy.

2021-03-15 | GSE147524 | GEO

Stabilizing the Proteomes of Acute Myeloid Leukemia Cells: Implications for Cancer Proteomics

Project description:Data dependent analysis of acute myeloid leukemia samples in the presence and absence of the serine protease inhibitor DFP

2023-07-26 | MSV000092526 | MassIVE

Shared Graft Versus Leukemia Minor Histocompatibility Antigens in DISCOVeRY-BMT

Project description:To predict shared graft versus leukemia minor histocompatibility antigens (mHAs) from the DISCOVeRY-BMT dataset. Via mass spectrometry, we then validated predicted mHAs in cell lines with the corresponding HLA allele and nonzero RNAseq reads corresponding to the source gene of the mHA.

2022-12-06 | GSE212013 | GEO

caArray_golub-00392: Gefitinib (Iressa) induces myeloid differentiation of acute myeloid leukemia

Project description:Cure rates for patients with acute myeloid leukemia (AML) remain low despite ever-increasing dose intensity of cytotoxic therapy. In an effort to identify novel approaches to AML therapy, we recently reported a new method of chemical screening based on the modulation of a gene expression signature of interest. We applied this approach to the discovery of AML-differentiation-promoting compounds. Among the compounds inducing neutrophilic differentiation was DAPH1 (4,5-dianilinophthalimide), previously reported to inhibit epidermal growth factor receptor (EGFR) kinase activity. Here we report that the Food and Drug Administration (FDA)-approved EGFR inhibitor gefitinib similarly promotes the differentiation of AML cell lines and primary patient-derived AML blasts in vitro. Gefitinib induced differentiation based on morphologic assessment, nitro-blue tetrazolium reduction, cell-surface markers, genome-wide patterns of gene expression, and inhibition of proliferation at clinically achievable doses. Importantly, EGFR expression was not detected in AML cells, indicating that gefitinib functions through a previously unrecognized EGFR-independent mechanism. These studies indicate that clinical trials testing the efficacy of gefitinib in patients with AML are warranted. golub-00392 Assay Type: Gene Expression Provider: Affymetrix Array Designs: HG-U133A, HG-U133A_2 Organism: Homo sapiens (ncbitax) Material Types: cell, total_RNA, synthetic_RNA, organism_part, whole_organism*Cell Types: Disease States: Acute Myeloid Leukemia, Normal, Acute Myeloid Leukemia

2015-05-16 | E-GEOD-68954 | biostudies-arrayexpress

lncRNA dependencies in acute myeloid leukemia

Project description:lncRNA dependencies in acute myeloid leukemia

| PRJNA354371 | ENA