Cathepsin G is broadly expressed in acute myeloid leukemia and is an effective immunotherapeutic target

Alatrash, Gheath; Garber, Haven R.; Zhang, M.; Sukhumalchandra, Pariya; Qiu, Yihua; Jakher, Haroon; Perakis, Alexander A.; Becker, Lisa; Yoo, Suk Young; Dwyer, Karen C.; Coombes, Kevin R.; Talukder, Amjad H.; John, Lisa S. St.; Senyukov, Vladimir; Lee, Dean A.; Сергеева, Анна; He, Hongchao; Ma, Qing; Armistead, Paul M.; Roszik, Jason; Mittendorf, Elizabeth A.; Molldrem, Jeffrey J.; Hawke, David H.; Lizee, Gregory; Kornblau, Steven M.

doi:10.1038/leu.2016.249

Cited by 22 publications

(28 citation statements)

References 14 publications

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“…HTR1E encodes a protein with G protein-coupled receptor activity and neurotransmitter receptor activity [ 35 ]. CTSG encodes a member of the peptidase S1 protein family, which is found broadly expressed in acute myeloid leukemia and may participate in the connective tissue remodeling at the site of inflammation [ 47 , 48 ].…”

Section: Discussionmentioning

confidence: 99%

The Important Role of Perituberal Tissue in Epileptic Patients with Tuberous Sclerosis Complex by the Transcriptome Analysis

Shao

Chang

2020

BioMed Research International

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Epilepsy is most common in patients with tuberous sclerosis complex (TSC). However, in addition to the challenging treatment, the pathogenesis of epilepsy is still controversial. To determine the transcriptome characteristics of perituberal tissue (PT) and clarify its role in the pathogenesis of epilepsy, GSE16969 was downloaded from the GEO database for further study by comprehensive bioinformatics analysis. Identification of differentially expressed genes (DEGs), functional enrichment analysis, construction of protein-protein interaction (PPI) network, and selection of Hub genes were performed using R language, Metascape, STRING, and Cytoscape, respectively. Comparing with cortical tuber (CT), 220 DEGs, including 95 upregulated and 125 downregulated genes, were identified in PT and mainly enriched in collagen-containing extracellular matrix and positive regulation of receptor-mediated endocytosis, as well as the pathways of ECM-receptor interaction and neuroactive ligand-receptor interaction. As for normal cortex (NC), 1549 DEGs, including 30 upregulated and 1519 downregulated genes, were identified and mainly enriched in presynapse, dendrite and axon, and also the pathways of dopaminergic synapse and oxytocin signaling pathway. In the PPI network, 4 hub modules were found between PT and CT, and top 5 hub modules were selected between PT and NC. C3, APLNR, ANXA2, CD44, CLU, CP, MCHR2, HTR1E, CTSG, APP, and GNG2 were identified as Hub genes, of which, C3, CD44, ANXA2, HTR1E, and APP were identified as Hub-BottleNeck genes. In conclusion, PT has the unique characteristics different from CT and NC in transcriptome and makes us further understand its importance in the TSC-associated epilepsy.

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Section: Discussionmentioning

confidence: 99%

The Important Role of Perituberal Tissue in Epileptic Patients with Tuberous Sclerosis Complex by the Transcriptome Analysis

Shao

Chang

2020

BioMed Research International

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“…Cells lines were validated at the MD Anderson Sequencing and Microarray Facility via short tandem repeat DNA fingerprinting and checked for mycoplasma via PCR (PromoKine). Raji cells were transduced with HLA-A*0201 as described previously using a lentiviral vector encoding HLA-A*02:01 ( 18 , 22 ). HLA-A2 expression was verified by flow cytometry prior to using the cell line.…”

Section: Methodsmentioning

confidence: 99%

“…We showed that CG is processed by AML blasts and that a number of human leukocyte antigen (HLA) class I peptides derived from CG were presented by AML. We also demonstrated that cytotoxic T lymphocytes (CTLs) that are expanded to target CG1 (FLLPTGAEA), a HLA-A2-restricted nonameric peptide derived from CG, eliminated AML in vitro and in vivo ( 17 , 18 ). Finally, we detected CTLs specific for CG1 in the peripheral blood of AML patients after allo-SCT ( 17 ).…”

Section: Introductionmentioning

confidence: 99%

“…CG is involved in host immunity, cleavage of inflammatory mediators, degradation of extracellular matrix components, antigen presentation, and leukemogenesis ( 13 – 16 ). We previously identified CG as a myeloid leukemia-associated antigen ( 17 , 18 ). We showed that CG is processed by AML blasts and that a number of human leukocyte antigen (HLA) class I peptides derived from CG were presented by AML.…”

Section: Introductionmentioning

confidence: 99%

“…Using mass spectrometry, we identified CG1 in the HLA class I-immunoprecipitated fraction from one patient with ALL ( 18 ). In addition to our studies, there have been three other reports that suggested CG expression in lymphoid leukemia.…”

Section: Introductionmentioning

confidence: 99%

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Cathepsin G Is Expressed by Acute Lymphoblastic Leukemia and Is a Potential Immunotherapeutic Target

et al. 2018

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Cathepsin G (CG) is a myeloid azurophil granule protease that is highly expressed by acute myeloid leukemia (AML) blasts and leukemia stem cells. We previously identified CG1 (FLLPTGAEA), a human leukocyte antigen-A2-restricted nonameric peptide derived from CG, as an immunogenic target in AML. In this report, we aimed to assess the level of CG expression in acute lymphoid leukemia (ALL) and its potential as an immunotherapeutic target in ALL. Using RT-PCR and western blots, we identified CG mRNA and protein, respectively, in B-ALL patient samples and cell lines. We also examined CG expression in a large cohort of 130 patients with ALL via reverse-phase protein array (RPPA). Our data show that CG is widely expressed by ALL and is a poor prognosticator. In addition to endogenous expression, we also provide evidence that CG can be taken up by ALL cells. Finally, we demonstrate that patient ALL can be lysed by CG1-specific cytotoxic T lymphocytes in vitro. Together, these data show high expression of CG by ALL and implicate CG as a target for immunotherapy in ALL.

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The extracellular matrix landscape in salivary gland carcinomas is defined by cellular differentiation via expression of three distinct protein modules

Arolt

Hoffmann

Nachtsheim

et al. 2023

The Journal of Pathology

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The extracellular matrix (ECM) is an integral part of the tumor microenvironment of carcinomas. Even though salivary gland carcinomas (SGCs) display a range of tumor cell differentiation and distinct extracellular matrices, their ECM landscape has not been characterized in depth. The ECM composition of 89 SGC primaries, 14 metastases, and 25 normal salivary gland tissues was assessed using deep proteomic profiling. Machine learning algorithms and network analysis were used to detect tumor groups and protein modules that explain specific ECM landscapes. Multimodal in situ studies to validate exploratory findings and to infer a putative cellular origin of ECM components were applied. We revealed two fundamental SGC ECM classes which align with the presence or absence of myoepithelial tumor differentiation. We describe the SGC ECM through three biologically distinct protein modules that are differentially expressed across ECM classes and cell types. The modules have a distinct prognostic impact on different SGC types. Since targeted therapy is rarely available for SGC, we used the proteomic expression profile to identify putative therapeutic targets. In summary, we provide the first extensive inventory of ECM components in SGC, a difficult‐to‐treat disease that encompasses tumors with distinct cellular differentiation. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

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Cathepsin G is broadly expressed in acute myeloid leukemia and is an effective immunotherapeutic target

Cited by 22 publications

References 14 publications

The Important Role of Perituberal Tissue in Epileptic Patients with Tuberous Sclerosis Complex by the Transcriptome Analysis

The Important Role of Perituberal Tissue in Epileptic Patients with Tuberous Sclerosis Complex by the Transcriptome Analysis

Cathepsin G Is Expressed by Acute Lymphoblastic Leukemia and Is a Potential Immunotherapeutic Target

The extracellular matrix landscape in salivary gland carcinomas is defined by cellular differentiation via expression of three distinct protein modules

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