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Multiple myeloma (MM) cells inhibit certain T-cell functions. We examined the expression of B7-H1 (PD-L1), a B7-related protein that inhibits T-cell responses, in CD138-purified plasma cells isolated from MM patients, monoclonal gammopathy of undetermined significance patients, and healthy donors. We observed that B7-H1 was expressed in most MM plasma(More)
B7-H1 (PD-L1) is a B7-related protein that inhibits T-cell responses. B7-H1 participates in the immunoescape of cancer cells and is also involved in the long-term persistence of leukemic cells in a mouse model of leukemia. B7-H1 can be constitutively expressed by cancer cells, but is also induced by various stimuli. Therefore, we examined the constitutive(More)
We developed a murine model of CNS disease to obtain a better understanding of the pathogenesis of CNS involvement in pre-B-cell acute lymphoblastic leukemia (ALL). Semiquantitative proteomic discovery-based approaches identified unique expression of asparaginyl endopeptidase (AEP), intercellular adhesion molecule 1 (ICAM1), and ras-related C3 botulinum(More)
Using proteins in a therapeutic context often requires engineering to modify functionality and enhance efficacy. We have previously reported that the therapeutic antileukemic protein macromolecule Escherichia coli L-asparaginase is degraded by leukemic lysosomal cysteine proteases. In the present study, we successfully engineered L-asparaginase to resist(More)
In the BCR/ABL DA1-3b mouse model of acute myelogenous leukemia, dormant tumor cells may persist in the host in a state of equilibrium with the CD8(+) CTL-mediated immune response by actively inhibiting T cells. Dormant tumor cells also show a progressive decrease of suppressor of cytokine signaling 1 (SOCS1) gene expression and a deregulation of the(More)
l-Asparaginase is a key therapeutic agent for treatment of childhood acute lymphoblastic leukemia (ALL). There is wide individual variation in pharmacokinetics, and little is known about its metabolism. The mechanisms of therapeutic failure with l-asparaginase remain speculative. Here, we now report that 2 lysosomal cysteine proteases present in(More)
From: Children’s Cancer Group, Institute of Cancer Sciences, Manchester Academic Health Sciences Centre, University of Manchester, United Kingdom; Manchester Centre for Cellular Metabolism, Institute of Cancer Sciences, Manchester Academic Health Sciences Centre, University of Manchester, United Kingdom; Tata Medical Center, Kolkata, India, Tata(More)
Despite the high cure rates in childhood acute lymphoblastic leukemia (ALL), relapsed ALL remains a significant clinical problem. Genetic heterogeneity does not adequately explain variations in response to therapy. The chemoprotective tumor microenvironment may additionally contribute to disease recurrence. This study identifies metabolic reprogramming of(More)
1Biomolecular Modelling Laboratory, Cancer Research UK London Research Institute, Lincoln’s Inn Fields Laboratories, London, United Kingdom; 2Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel; 3Department of Bioinformatics and Telemedicine, Jagiellonian University, Collegium Medicum, Krakow, Poland; and 4Cancer Research UK Children’s(More)
In the BCR/ABL DA1-3b mouse model of acute myelogenous leukemia, dormant tumor cells may persist in the host in a state of equilibrium with the CD8 CTL-mediated immune response by actively inhibiting T cells. Dormant tumor cells also show a progressive decrease of suppressor of cytokine signaling 1 (SOCS1) gene expression and a deregulation of the(More)