Non-Hodgkin Lymphomas: Malignancies Arising from Mature B Cells

Shingleton, Jennifer R.; Wang, Jie; Baloh, Carolyn; Dave, Tushar; Davis, Nicholas S.; Happ, Lanie E.; Jadi, Othmane; Kositsky, Rachel; Li, Xiang; Love, Cassandra; Panea, Razvan; Qin, Qiu; Reddy, Anupama; Singhi, Naina; Smith, Eileen; Thakkar, Devang; Davé, Sandeep S.

doi:10.1101/cshperspect.a034843

Cited by 5 publications

(3 citation statements)

References 90 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Lymphomas are clonal malignancies commonly divided as Hodgkin lymphoma (HL), which is derived from B cells and characterized by an inflammatory microenvironment, or non‐Hodgkin lymphoma (NHL), which is derived from T‐, B‐ or natural killer cells 1–5 . These malignancies are first‐line treated with chemotherapy, radiotherapy, or mAbs targeting CD19, CD20 and other markers 1,3,6,7 . About 60%–70% of refractory/relapsed HL patients respond to immune checkpoint inhibitor treatments, possibly due to increased expression of PD‐1 ligands and an inflammatory lymphoma microenvironment 6,8–10 .…”

Section: Introductionmentioning

confidence: 99%

Antibody targeting of surface P‐selectin glycoprotein ligand 1 leads to lymphoma apoptosis and tumorigenesis inhibition

Pereira,

Ferreira,

dos Santos

2024

Hematological Oncology

View full text Add to dashboard Cite

Lymphomas are a heterogeneous group of diseases that originate from T, B or natural killer cells. Lymphoma treatment is based on chemotherapy, radiotherapy, and monoclonal antibody (mAb) or other immunotherapies. The P‐selectin glycoprotein ligand 1 (PSGL‐1) is expressed at the surface of hematological malignant cells and has been shown to have a pro‐oncogenic role in multiple myeloma and lymphoma. Here, we investigated the expression and therapeutic potential of PSGL‐1 in T and B cell lymphomas. By flow cytometry analysis, we found that PSGL‐1 was expressed in both T and B cell‐derived lymphoma cell lines but generally at higher levels in T cell lymphoma cell lines. For most T and B cell‐derived lymphoma cell lines, in vitro targeting with the PL1 mAb, which recognizes the PSGL‐1 N‐terminal extracellular region and blocks functional interactions with selectins, resulted in reduced cell viability. The PL1 mAb pro‐apoptotic activity was shown to be dose‐dependent, to be linked to increased ERK kinase phosphorylation, and to be dependent on the MAP kinase signaling pathway. Importantly, anti‐PSGL‐1 treatment of mice xenografted with the HUT‐78 cutaneous T‐cell lymphoma cell line resulted in decreased tumor growth, had no effect on in vivo proliferation, but increased the levels of apoptosis in tumors. Anti‐PSGL‐1 treatment of mice xenografted with a Burkitt lymphoma cell line that was resistant to anti‐PSGL‐1 treatment in vitro, had no impact on tumorigenesis. These findings show that PSGL‐1 antibody targeting triggers lymphoma cell apoptosis and substantiates PSGL‐1 as a potential target for lymphoma therapy.

show abstract

Section: Introductionmentioning

confidence: 99%

Antibody targeting of surface P‐selectin glycoprotein ligand 1 leads to lymphoma apoptosis and tumorigenesis inhibition

Pereira,

Ferreira,

dos Santos

2024

Hematological Oncology

View full text Add to dashboard Cite

show abstract

“…[1][2][3][4][5] These malignancies are first-line treated with chemotherapy, radiotherapy, or mAbs targeting CD19, CD20 and other markers. 1,3,6,7 About 60-70% of refractory/relapsed HL patients respond to immune checkpoint inhibitor treatments, possibly due to increased expression of PD-1 ligands and an inflammatory lymphoma microenvironment. 6,[8][9][10] However, NHL are often resistant to checkpoint inhibitor blockade therapies, with approximately 20-40% response obtained in clinical trials.…”

Section: Introductionmentioning

confidence: 99%

Antibody targeting of surface PSGL-1 glycoprotein leads to lymphoma apoptosis and tumorigenesis inhibition

Pereira,

Ferreira,

dos Santos

2024

Preprint

View full text Add to dashboard Cite

Lymphomas are a heterogeneous group of diseases that originate from T, B or natural killer (NK) cells. Lymphoma treatment is based on chemotherapy, radiotherapy, and monoclonal antibody (mAb) or other immunotherapies. The P-selectin glycoprotein ligand 1 (PSGL-1) is expressed at the surface of hematological malignant cells and has been shown to have a pro-oncogenic role in multiple myeloma and lymphoma. Here, we investigated the expression and therapeutic potential of PSGL-1 in T and B cell lymphomas. By flow cytometry analysis, we found that PSGL-1 was expressed in both T and B cell-derived lymphoma cell lines but generally at higher levels in T cell lymphoma cell lines. For most T and B cell-derived lymphoma cell lines, in vitro targeting with the PL1 mAb, which recognizes the PSGL-1 N-terminal extracellular region and blocks functional interactions with selectins, resulted in reduced cell viability. The PL1 mAb pro-apoptotic activity was shown to be dose-dependent, to be linked to increased ERK kinase phosphorylation, and to be dependent on the MAP kinase signaling pathway. Importantly, anti-PSGL-1 treatment of mice xenografted with the HUT-78 cutaneous T-cell lymphoma (CTCL) cell line resulted in decreased tumor growth, had no effect on in vivo proliferation, but increased the levels of apoptosis in tumors. Anti-PSGL-1 treatment of mice xenografted with a Burkitt lymphoma (BL) cell line that was resistant to anti-PSGL-1 treatment in vitro, had no impact on tumorigenesis. These findings show that PSGL-1 antibody targeting triggers lymphoma cell apoptosis and substantiates PSGL-1 as a potential target for lymphoma therapy.

show abstract

“…The most common of these disorders include chronic myeloid leukemia (CML), chronic lymphocytic leukemia (CLL), multiple myeloma (MM), and B-cell non-Hodgkin’s lymphomas (B-cell NHLs) [ 1 , 2 ]. Historically, the mainstays of therapy for these diseases have been chemotherapy, radiotherapy, and bone marrow transplantation (BMT) [ 3 , 4 , 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Pathobiology and Therapeutic Relevance of GSK-3 in Chronic Hematological Malignancies

Martelli

Paganelli

Evangelisti

et al. 2022

Cells

View full text Add to dashboard Cite

Glycogen synthase kinase-3 (GSK-3) is an evolutionarily conserved, ubiquitously expressed, multifunctional serine/threonine protein kinase involved in the regulation of a variety of physiological processes. GSK-3 comprises two isoforms (α and β) which were originally discovered in 1980 as enzymes involved in glucose metabolism via inhibitory phosphorylation of glycogen synthase. Differently from other proteins kinases, GSK-3 isoforms are constitutively active in resting cells, and their modulation mainly involves inhibition through upstream regulatory networks. In the early 1990s, GSK-3 isoforms were implicated as key players in cancer cell pathobiology. Active GSK-3 facilitates the destruction of multiple oncogenic proteins which include β-catenin and Master regulator of cell cycle entry and proliferative metabolism (c-Myc). Therefore, GSK-3 was initially considered to be a tumor suppressor. Consistently, GSK-3 is often inactivated in cancer cells through dysregulated upstream signaling pathways. However, over the past 10–15 years, a growing number of studies highlighted that in some cancer settings GSK-3 isoforms inhibit tumor suppressing pathways and therefore act as tumor promoters. In this article, we will discuss the multiple and often enigmatic roles played by GSK-3 isoforms in some chronic hematological malignancies (chronic myelogenous leukemia, chronic lymphocytic leukemia, multiple myeloma, and B-cell non-Hodgkin’s lymphomas) which are among the most common blood cancer cell types. We will also summarize possible novel strategies targeting GSK-3 for innovative therapies of these disorders.

show abstract

Non-Hodgkin Lymphomas: Malignancies Arising from Mature B Cells

Cited by 5 publications

References 90 publications

Antibody targeting of surface P‐selectin glycoprotein ligand 1 leads to lymphoma apoptosis and tumorigenesis inhibition

Antibody targeting of surface P‐selectin glycoprotein ligand 1 leads to lymphoma apoptosis and tumorigenesis inhibition

Antibody targeting of surface PSGL-1 glycoprotein leads to lymphoma apoptosis and tumorigenesis inhibition

Pathobiology and Therapeutic Relevance of GSK-3 in Chronic Hematological Malignancies

Contact Info

Product

Resources

About