Abstract
Mature B-cell non-Hodgkin lymphoma (B-NHL) constitutes a group of heterogeneous malignant lymphoproliferative diseases ranging from indolent to highly aggressive forms. Although the survival after chemo-immunotherapy treatment of mature B-NHL has increased over the last years, many patients relapse or remain refractory due to drug resistance, presenting an unfavorable prognosis. Hence, there is an urgent need to identify new prognostic markers and therapeutic targets. Podocalyxin (PODXL), a sialomucin overexpressed in a variety of tumor cell types and associated with their aggressiveness, has been implicated in multiple aspects of cancer progression, although its participation in hematological malignancies remains unexplored. New evidence points to a role for PODXL in mature B-NHL cell proliferation, survival, migration, drug resistance, and metabolic reprogramming, as well as enhanced levels of PODXL in mature B-NHL. Here, we review the current knowledge on the contribution of PODXL to tumorigenesis, highlighting and discussing its role in mature B-NHL progression.
Highlights
Non-Hodgkin lymphoma (NHL) represents the most common hematological malignancy in adults worldwide and accounts for approximately 90% of all diagnosed lymphomas in western countries, with B cell-NHL (B-NHL) being more frequent (85%–90%) than T-cell or natural killer (NK)-cellNHL [1,2]
In Raji Burkitt lymphoma cells, we showed that ectopic overexpression of PODXL enhanced cell proliferation and colony formation [27]
We have shown that forced expression of PODXL in Raji Burkitt lymphoma cells increased cell survival upon treatment with obinutuzumab [27], a novel type II glycoengineered humanized anti-CD20 monoclonal antibody with superior ability to induce direct, non-complement dependent cell death and enhanced antibody-dependent cellular cytotoxicity (ADCC) compared to rituximab [124,125]
Summary
Non-Hodgkin lymphoma (NHL) represents the most common hematological malignancy in adults worldwide and accounts for approximately 90% of all diagnosed lymphomas in western countries, with B cell-NHL (B-NHL) being more frequent (85%–90%) than T-cell or natural killer (NK)-cellNHL [1,2]. B-NHL consists of a heterogeneous group of lymphoproliferative malignancies that arise from lymphoid tissue B cells at varying stages of maturation and can spread to other organs, encompassing more than 40 neoplasm subtypes both molecular and clinically different [4]. They are currently classified according to the 2016 revision of the World Health Organization (WHO) classification of lymphoid neoplasms based on cell linage and pathological, genetic, immunophenotypic, and clinical features [4].
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