The predominant usage of VH4-34 and V3-21 and reports of stereotyped CDR3s suggest a shared antigenic target of B-cell receptors (BCR) from mantle cell lymphomas (MCL). To identify the target antigens of MCL-BCRs, BCRs from 21 patients and seven MCL cell lines were recombinantly expressed and used for antigen screening. The BCRs from 8/21 patients and 2/7 MCL cell lines reacted specifically with the autoantigen low-density lipoprotein receptor-related protein-associated protein 1 (LRPAP1). High-titered and light chain-restricted anti-LRPAP1 serum antibodies were found in MCL patients, but not in controls. LRPAP1 induced proliferation by BCR pathway activation, while an LRPAP1-ETA' toxin-conjugate specifically killed MCL cells with LRPAP1-specific BCRs. Our results suggest a role of LRPAP1 in lymphomagenesis and maintenance of a considerable proportion of MCL cases by chronic autoantigenic stimulation, likely evolving from a chronic autoreactive B-cell response. Importantly, LRPAP1 can be used for a novel therapeutic approach that targets MCL with LRPAP1-reactive BCRs with high specificity.
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http://dx.doi.org/10.1038/s41375-018-0182-1 | DOI Listing |
Front Oncol
December 2024
Penn State Hershey Cancer Institute, Pennsylvania State University College of Medicine, Hershey, PA, United States.
Br J Haematol
December 2024
Hematology, School of Medicine, Università degli Studi di Milano, Milan, Italy.
Brexucabtagene autoleucel (brexu-cel) has revolutionized the treatment of patients affected by mantle cell lymphomas. In this prospective, observational multicentre study, we evaluated 106 patients, with longitudinal brexu-cel kinetics in peripheral blood monitored in 61 of them. Clinical outcomes and toxicities are consistent with previous real-world evidence studies.
View Article and Find Full Text PDFLeuk Lymphoma
December 2024
Department of Clinical Haematology, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, Australia.
FEBS Lett
December 2024
INSERM U978, Bobigny, France.
Cell adhesion is warranted by proteins that are crucial for the maintenance of tissue integrity and homeostasis. Most of these proteins behave as receptors to link adhesion to the control of cell survival and their expression or regulation are often altered in cancers. B-cell malignancies do not evade this principle as they are sustained in relapsed niches by interacting with the microenvironment that includes cells and their secreted factors.
View Article and Find Full Text PDFInt J Hematol Oncol Stem Cell Res
October 2024
Department of Endocrinology and Internal Medicine, Tahar Sfar University Hospital, Mahdia, Tunisia.
Primary vertebral lymphoma is an exceedingly rare entity. We hereby report a case of a 67-year-old male who presented to our department with fever, weight loss, and progressively worsening lower back pain radiating to the right hip. Physical examination showed pain on percussion of the dorsal and lumbar spine and tenderness on palpation of the right upper thigh area.
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