Dataset Information

Aberrant CD3-Positive, CD8-Low, CD7-Negative Lymphocytes May Appear During Viral Infections and Mimic Peripheral T-Cell Lymphoma.

ABSTRACT: Flow cytometry (FC) facilitates diagnosis of peripheral T-cell non-Hodgkin lymphoma (T-NHL), but overlapping features between reactive and neoplastic T-cell proliferations often hamper a rapid assessment. One hundred forty peripheral blood samples submitted to diagnostic FC for T-cell immunophenotyping were retrospectively analyzed. A T-cell population with a conspicuous aberrant surface epitope expression pattern was observed in 18 cases and diagnostic follow up was performed. The aberrant T-cell population exhibited a low scatter profile, a CD7-negative/low, CD8-low and CD3-positive immunophenotype, and monoclonal T-cell receptor expansion. T-NHL was ruled out by follow up in all cases. Epstein-Barr virus infection was diagnosed in 12 cases, cytomegalovirus infection in three cases; one patient had been vaccinated. The irregular subpopulation disappeared spontaneously within days or weeks. We describe a novel peripheral blood T-cell subpopulation with a low light scatter and CD8-low, CD7-negative/low and CD3-positive marker expression profile, which indicates reactive T-cell expansion in patients who present with peripheral lymphadenopathy and/or B symptoms.

SUBMITTER: Klameth A

PROVIDER: S-EPMC7235783 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Aberrant CD3-Positive, CD8-Low, CD7-Negative Lymphocytes May Appear During Viral Infections and Mimic Peripheral T-Cell Lymphoma.

Klameth Andreas A Neubauer Andreas A Keller Christian C Aepinus Christian C Kaiser Ulrich U Hoffmann Jörg J Brendel Cornelia C

Diagnostics (Basel, Switzerland) 20200407 4

Flow cytometry (FC) facilitates diagnosis of peripheral T-cell non-Hodgkin lymphoma (T-NHL), but overlapping features between reactive and neoplastic T-cell proliferations often hamper a rapid assessment. One hundred forty peripheral blood samples submitted to diagnostic FC for T-cell immunophenotyping were retrospectively analyzed. A T-cell population with a conspicuous aberrant surface epitope expression pattern was observed in 18 cases and diagnostic follow up was performed. The aberrant T-ce ...[more]

PMID: 32272749

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Project description:BackgroundPancreatic ductal adenocarcinomas (PDAC) have heterogeneous tumor microenvironments relatively devoid of infiltrating immune cells. We aimed to quantitatively assess infiltrating CD3+ and CD8+ lymphocytes in a treatment-naïve patient cohort and assess associations with overall survival and microenvironment inflammatory proteins.MethodsTissue microarrays were immunohistochemically stained for CD3+ and CD8+ lymphocytes and quantitatively assessed using QuPath. Levels of inflammation-associated proteins were quantified by multiplexed, enzyme-linked immunosorbent assay panels on matching tumor and tissue samples.ResultsOur findings revealed a significant increase in both CD3+ and CD8+ lymphocytes populations in PDAC compared with non-PDAC tissue, except when comparing CD8+ percentages in PDAC versus intraductal papillary mucinous neoplasms (IPMN) (p = 0.5012). Patients with quantitatively assessed CD3+ low tumors (lower 50%) had shorter survival (median 273 days) compared to CD3+ high tumors (upper 50%) with a median overall survival of 642.5 days (p = 0.2184). Patients with quantitatively assessed CD8+ low tumors had significantly shorter survival (median 240 days) compared to CD8+ high tumors with a median overall survival of 1059 days (p = 0.0003). Of 41 proteins assessed in the inflammation assay, higher levels of IL-1B and IL-2 were significantly associated with decreased CD3+ infiltration (r = -0.3704, p = 0.0187, and r = -0.4275, p = 0.0074, respectively). Higher levels of IL-1B were also significantly associated with decreased CD8+ infiltration (r = -0.4299, p = 0.0045), but not IL-2 (r = -0.0078, p = 0.9616). Principal component analysis of the inflammatory analytes showed diverse inflammatory responses in PDAC.ConclusionIn this work, we found a marked heterogeneity in infiltrating CD3+ and CD8+ lymphocytes and individual inflammatory responses in PDAC. Future mechanistic studies should explore personalized therapeutic strategies to target the immune and inflammatory components of the tumor microenvironment.

Project description:DNA methyltransferase 3A (DNMT3A) is an enzyme involved in DNA methylation that is frequently mutated in human hematologic malignancies. We have previously shown that inactivation of Dnmt3a in hematopoietic cells results in chronic lymphocytic leukemia in mice. Here we show that 12% of Dnmt3a-deficient mice develop CD8+ mature peripheral T cell lymphomas (PTCL) and 29% of mice are affected by both diseases. 10% of Dnmt3a+/- mice develop lymphomas, suggesting that Dnmt3a is a haploinsufficient tumor suppressor in PTCL. DNA methylation was deregulated genome-wide with 10-fold more hypo- than hypermethylated promoters and enhancers, demonstrating that hypomethylation is a major event in the development of PTCL. Hypomethylated promoters were enriched for binding sites of transcription factors AML1, NF-κB and OCT1, implying the transcription factors potential involvement in Dnmt3a-associated methylation. Whereas 71 hypomethylated genes showed an increased expression in PTCL, only 3 hypermethylated genes were silenced, suggesting that cancer-specific hypomethylation has broader effects on the transcriptome of cancer cells than hypermethylation. Interestingly, transcriptomes of Dnmt3a+/- and Dnmt3aΔ/Δ lymphomas were largely conserved and significantly overlapped with those of human tumors. Importantly, we observed downregulation of tumor suppressor p53 in Dnmt3a+/- and Dnmt3aΔ/Δ lymphomas as well as in pre-tumor thymocytes from 9 months old but not 6 weeks old Dnmt3a+/- tumor-free mice, suggesting that p53 downregulation is chronologically an intermediate event in tumorigenesis. Decrease in p53 is likely an important event in tumorigenesis because its overexpression inhibited proliferation in mouse PTCL cell lines, suggesting that low levels of p53 are important for tumor maintenance. Altogether, our data link the haploinsufficient tumor suppressor function of Dnmt3a in the prevention of mouse mature CD8+ PTCL indirectly to a bona fide tumor suppressor of T cell malignancies p53.

Dataset Information

Aberrant CD3-Positive, CD8-Low, CD7-Negative Lymphocytes May Appear During Viral Infections and Mimic Peripheral T-Cell Lymphoma.

Publications

Aberrant CD3-Positive, CD8-Low, CD7-Negative Lymphocytes May Appear During Viral Infections and Mimic Peripheral T-Cell Lymphoma.

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