TY - JOUR
T1 - Cathepsin G is expressed by acute lymphoblastic leukemia and is a potential immunotherapeutic target
AU - Khan, Maliha
AU - Carmona, Selena
AU - Sukhumalchandra, Pariya
AU - Roszik, Jason
AU - Philips, Anne
AU - Perakis, Alexander A.
AU - Kerros, Celine
AU - Zhang, Mao
AU - Qiao, Na
AU - St. John, Lisa S.
AU - Zope, Madhushree
AU - Goldberg, Jonathan
AU - Qazilbash, Mariam
AU - Jakher, Haroon
AU - Clise-Dwyer, Karen
AU - Qiu, Yihua
AU - Mittendorf, Elizabeth A.
AU - Molldrem, Jeffrey J.
AU - Kornblau, Steven M.
AU - Alatrash, Gheath
N1 - Publisher Copyright:
© 2018 Khan, Carmona, Sukhumalchandra, Roszik, Philips, Perakis, Kerros, Zhang, Qiao, John, Zope, Goldberg, Qazilbash, Jakher, Clise-Dwyer, Qiu, Mittendorf, Molldrem, Kornblau and Alatrash.
PY - 2018/1/25
Y1 - 2018/1/25
N2 - 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.
AB - 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.
KW - Acute lymphoblastic leukemia
KW - Antigens
KW - Cathespin G
KW - Cross-presentation
KW - Immunotherapy
KW - Nonameric peptide
KW - Serine proteases
KW - Targeted therapy
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U2 - 10.3389/fimmu.2017.01975
DO - 10.3389/fimmu.2017.01975
M3 - Article
C2 - 29422892
AN - SCOPUS:85041125986
SN - 1664-3224
VL - 8
JO - Frontiers in immunology
JF - Frontiers in immunology
IS - JAN
M1 - 1975
ER -