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

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2018 Feb 10

PMID 29422892

Citations 14

Authors

Maliha Khan

Selena Carmona

Pariya Sukhumalchandra

Jason Roszik

Anne Philips

Alexander A Perakis

Celine Kerros

Mao Zhang

Na Qiao

Lisa S St John

Madhushree Zope

Jonathan Goldberg

Mariam Qazilbash

Haroon Jakher

Karen Clise-Dwyer

Yihua Qiu

Elizabeth A Mittendorf

Jeffrey J Molldrem

Steven M Kornblau

Gheath Alatrash

Affiliations

Soon will be listed here.

Abstract

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 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 . Together, these data show high expression of CG by ALL and implicate CG as a target for immunotherapy in ALL.

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