CD38 expression is an important prognostic marker in diffuse large B‐cell lymphoma

Wada, Fumiya; Shimomura, Yoshimitsu; Yabushita, Tomohiro; Yamashita, Daisuke; Ohno, Aya; Imoto, Hiroharu; Maruoka, Hayato; Hara, Shigeo; Ishikawa, Takayuki

doi:10.1002/hon.2904

Cited by 9 publications

(5 citation statements)

References 26 publications

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“…Studies using flow cytometry have shown the association of the intensity of CD38 expression with more aggressive DLBCL variants or high CD38 expression to be an independent predictor of poor outcomes in de novo DLBCL. 21,22 This case could not be categorised into known variants of CD20 negative DLBCL and in the literature there are few reports describing such new cases of DLBCL, 20,23,24 Nakatsuka et al reported an EBV-positive DLBCL case that was negative for various B-cell (CD19, CD20, CD79a, CD38, CD138) and T-cell (CD3, CD4, CD5, CD8) markers. 20 This case was positive only for Oct-2 and BOB-1.…”

Section: Discussionmentioning

confidence: 99%

Primary Nodal Unclassifiable CD20 Negative Diffuse Large B-cell Lymphoma With Dual IgK and TCR Gene Rearrangement: A Diagnostic Challenge

Hadžisejdić

Klarica

Babarović

et al. 2023

Clin Med�Insights�Pathol

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Non-Hodgkin lymphomas are most frequently classified based on the lineage marker expression. However, lymphomas with aberrant marker expression as well as monoclonal IgH/IgΚ and TCR gene rearrangements may co-exist which can be misleading and confusing. Primary CD20 negative diffuse large B-cell lymphomas (DLBCL) represent a rare entity, and they account for 1% to 3% of cases. However, some CD20 negative DLBCLs could not be classified into known variants, creating both diagnostic and therapeutic dilemma’s. Primary CD20 negative DLBCL are more likely to have a non-germinal centre subtype, a higher proliferation index, more frequent extra-nodal involvement, a poorer response, and poorer prognosis to conventional treatment compared to CD20 positive DLBCL. A 66- year-old postmenopausal lady, presented with palpable, bilateral neck lymphadenopathy and difficulty swallowing. She also had left leg lymphoedema, poor appetited, fatigue and weight loss. Her symptoms lasted approximately 1 month. After histological, immunohistochemical and clonality analysis of the lymph node the patient was diagnosed with primary nodal CD20 and PAX-5 negative DLBCL with dual immunoglobulin light-chain kappa ( IgK) and T-cell receptor ( TCR) gene rearrangement. This unusual and unique case presented a diagnostic challenge because it was CD20 and PAX-5 negative, had dual IgK and TCR gene rearrangement and, it could not be classified within the known and well established CD20 negative DLBCL variants. Describing such cases emphasises the fact that lymphomas unclassifiable within known variants of CD20 negative DLBCL do exist and that range and heterogeneity of CD20 negative DLBCL continues to evolve, and pathologist should be aware of these uncommon, atypical mature B-cell neoplasms.

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Section: Discussionmentioning

confidence: 99%

Primary Nodal Unclassifiable CD20 Negative Diffuse Large B-cell Lymphoma With Dual IgK and TCR Gene Rearrangement: A Diagnostic Challenge

Hadžisejdić

Klarica

Babarović

et al. 2023

Clin Med�Insights�Pathol

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“…Of particular note, CD38 is highly expressed in two naïve B cell subsets that are only enriched in DHL patients. As a type II transmembrane glycoprotein, the highly expressed CD38 is an important factor in the poor prognosis of B cell lymphoma [ 32 , 33 ]. This suggests that CD38 could be a biomarker for diagnosis (distinguishing from other DLBCL subtypes) or prognosis of DHL.…”

Section: Discussionmentioning

confidence: 99%

Peripheral immune cell profiling of double-hit lymphoma by mass cytometry

Lei

et al. 2023

BMC Cancer

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Background Double-hit or Triple-hit lymphoma (DHL/THL) is a subset of high-grade B cell lymphoma harboring rearrangements of MYC and BCL2 and/or BCL6, and usually associate with aggressive profile, while current therapies tend to provide poor clinical outcomes and eventually relapsed. Further explorations of DHL at cellular and molecular levels are in demand to offer guidance for clinical activity. Methods We collected the peripheral blood of DHL patients and diffused large B cell lymphoma (DLBCL) patients from single institute and converted them into PBMC samples. Mass cytometry was then performed to characterize these samples by 42 antibody markers with samples of healthy people as control. We divided the immune cell subtypes based on the expression profile of surface antigens, and the proportion of each cell subtype was also analyzed. By comparing the data of the DLBCL group and the healthy group, we figured out the distinguished immune cell subtypes of DHL patients according to their abundance and marker expression level. We further analyzed the heterogeneity of DHL samples by pairwise comparison based on clinical characteristics. Results We found double-positive T cells (DPT) cells were in a significantly high percentage in DHL patients, whereas the ratio of double-negative T cells (DNT) was largely reduced in patients. Besides, CD38 was uniquely expressed at a high level on some naïve B cells of DHL patients, which could be a marker for the diagnosis of DHL (distinguishing from DLBCL), or even be a drug target for the treatment of DHL. In addition, we illustrated the heterogeneity of DHL patients in terms of immune cell landscape, and highlighted TP53 as a major factor that contributes to the heterogeneity of the T cells profile. Conclusion Our study demonstrated the distinct peripheral immune cell profile of DHL patients by contrast to DLBCL patients and healthy people, as well as the heterogeneity within the DHL group, which could provide valuable guidance for the diagnosis and treatment of DHL.

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“…CD38 expression is abnormally high in DLBCL and can be detected in 80% of the cases [ 22 ]. Expression of CD38 on the surface appears to correlate with aggressiveness of the tumor and, in de novo DLBCL, high CD38 expression is associated with significantly worse progression-free survival and poor overall survival [ 13 , 76 ]. There have been no oncogenic mechanisms directly attributed to CD38 in DLBCL so far; however, its expression on aggressive variants of DLBCL suggests that it may support a proliferative phenotype.…”

Section: Cd38-mediated Tumor-promoting Mechanisms and Expression In H...mentioning

confidence: 99%

“…Enhanced expression of the CD38 membrane protein has also been reported in other aggressive hematological malignancies, including chronic lymphocytic leukemia (CLL), T-cell acute lymphoblastic leukemia (T-ALL), diffuse large B-cell lymphomas (DLBCL), and T and NK lymphomas (NKTL) [ 13 , 14 , 15 , 16 , 17 ]. This elevated CD38 expression has been associated with poorer prognosis and a more aggressive cancer phenotype, which is an outcome of the cancer cell hijacking underlying CD38-driven functions to create both a pro-tumoral extracellular environment and a cancer-permissive intracellular milieu [ 18 , 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular Determinants Underlying the Anti-Cancer Efficacy of CD38 Monoclonal Antibodies in Hematological Malignancies

Mustafa

Azaman

et al. 2022

Biomolecules

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CD38 was first discovered as a T-cell antigen and has since been found ubiquitously expressed in various hematopoietic cells, including plasma cells, NK cells, B cells, and granulocytes. More importantly, CD38 expression levels on malignant hematopoietic cells are significantly higher than counterpart healthy cells, thus presenting itself as a promising therapeutic target. In fact, for many aggressive hematological cancers, including CLL, DLBCL, T-ALL, and NKTL, CD38 expression is significantly associated with poorer prognosis and a hyperproliferative or metastatic phenotype. Studies have shown that, beyond being a biomarker, CD38 functionally mediates dysregulated survival, adhesion, and migration signaling pathways, as well as promotes an immunosuppressive microenvironment conducive for tumors to thrive. Thus, targeting CD38 is a rational approach to overcoming these malignancies. However, clinical trials have surprisingly shown that daratumumab monotherapy has not been very effective in these other blood malignancies. Furthermore, extensive use of daratumumab in MM is giving rise to a subset of patients now refractory to daratumumab treatment. Thus, it is important to consider factors modulating the determinants of response to CD38 targeting across different blood malignancies, encompassing both the transcriptional and post-transcriptional levels so that we can diversify the strategy to enhance daratumumab therapeutic efficacy, which can ultimately improve patient outcomes.

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CD38 expression is an important prognostic marker in diffuse large B‐cell lymphoma

Cited by 9 publications

References 26 publications

Primary Nodal Unclassifiable CD20 Negative Diffuse Large B-cell Lymphoma With Dual IgK and TCR Gene Rearrangement: A Diagnostic Challenge

Primary Nodal Unclassifiable CD20 Negative Diffuse Large B-cell Lymphoma With Dual IgK and TCR Gene Rearrangement: A Diagnostic Challenge

Peripheral immune cell profiling of double-hit lymphoma by mass cytometry

Molecular Determinants Underlying the Anti-Cancer Efficacy of CD38 Monoclonal Antibodies in Hematological Malignancies

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