Abnormal immunophenotype of the T‐cell‐receptor beta Chain in follicular‐helper T cells of angioimmunoblastic T‐cell lymphoma

Mao, Zhuo; Surowiecka, M.; Linden, Michael A.; Singleton, Timothy P.

doi:10.1002/cyto.b.21229

Cited by 4 publications

(2 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A monoclonal T-cell configuration was observed in over 75% of AITL patients 29 – 33 . Later on, Mao et al 34 demonstrated that AITL Tfh cells contain a clonal V segment of the TCRβ chain. Importantly, also the B-cell component of the tumor associated with the Tfh can show clonal rearrangements of the BCR 30 .…”

Section: Angioimmunoblastic T-cell Lymphoma: a Challenging Complex Mamentioning

confidence: 99%

New preclinical models for angioimmunoblastic T-cell lymphoma: filling the GAP

et al. 2020

View full text Add to dashboard Cite

Mouse models are essential to study and comprehend normal and malignant hematopoiesis. The ideal preclinical model should mimic closely the human malignancy. This means that these mice should recapitulate the clinical behavior of the human diseases such as cancer and therapeutic responses with high reproducibility. In addition, the genetic mutational status, the cell phenotype, the microenvironment of the tumor and the time until tumor development occurs, should be mimicked in a preclinical model. This has been particularly challenging for human angioimmunoblastic lymphoma (AITL), one of the most prominent forms of peripheral T-cell lymphomas. A complex network of interactions between AITL tumor cells and the various cells of the tumor microenvironment has impeded the study of AITL pathogenesis in vitro. Very recently, new mouse models that recapitulate faithfully the major features of human AITL disease have been developed. Here, we provide a summary of the pathology, the transcriptional profile and genetic and immune-phenotypic features of human AITL. In addition, we give an overview of preclinical models that recapitulate more or less faithfully human AITL characteristics and pathology. These recently engineered mouse models were essential in the evaluation of novel therapeutic agents for possible treatment of AITL, a malignancy in urgent need of new treatment options. Angioimmunoblastic T-cell lymphoma: a challenging complex malignancy Clinical aspects Angioimmunoblastic T-cell lymphoma (AITL) belongs since 2016 after revision of the world health organization (WHO) classification to the nodal T-cell lymphomas with follicular helper T-cell (Tfh) phenotype 1. AITL is a rare, aggressive lymphoma with little treatment options. Overall survival is generally poor with a five-year median survival rate of 32% 2,3. It represents only 1-2% of the non-Hodgkin's lymphomas. However, AITL appears to be the most prevalent PTCL, representing up to 35% of the noncutaneous peripheral T-cell lymphomas 2,4-6. AITL pathology develops late in life with a median age at onset of 59-65 years and patients display a generalized lymphoadenopathy 7,8. Seventy percent of the patients have bone marrow involvement and unfortunately early stage detection of AITL is very uncommon (10%) 9. Disease symptoms resemble closely an infection inducing immunologic hyper-activation (fever, rash, loss of weight, hemolytic anemia 2,5) (Fig. 1). AITL has particular clinical and pathological features, associated with splenomegaly, hepatomegaly and enlarged lymph nodes showing effacement of normal architecture and appearance of endothelial venules 3 (Fig. 1). Other typical clinical manifestation of AITL are cutaneous lesions also called skin rash in 20-50% of the patients and accumulation of abdominal ascites 5,10-13. These patients often test positive for autoimmunity including detection of rheumatoid factor, anti-smooth muscle, and nuclear autoantibodies 14. They also present a general increase in immunoglobulins called hypergammaglobulemia (30%) 7,12 .

show abstract

Section: Angioimmunoblastic T-cell Lymphoma: a Challenging Complex Mamentioning

confidence: 99%

New preclinical models for angioimmunoblastic T-cell lymphoma: filling the GAP

et al. 2020

View full text Add to dashboard Cite

show abstract

“…The TCRα and β loci are too complex and cumbersome for routine DNA clonal analyses, but flow cytometry can also detect TCRβ gene usage and thus imply clonality 9 , 10 . However, these approaches are also limited by the lack of sequence information.…”

Section: Introductionmentioning

confidence: 99%

Assessment of T-cell receptor repertoire and clonal expansion in peripheral T-cell lymphoma using RNA-seq data

Gong

Wang

Zhang

et al. 2017

Sci Rep

View full text Add to dashboard Cite

T-cell clonality of peripheral T-cell lymphoma (PTCL) is routinely evaluated with a PCR-based method using genomic DNA. However, there are limitations with this approach. The purpose of this study was to determine the utility of RNA-seq for assessing T-cell clonality and T-cell antigen receptor (TCR) repertoire of the neoplastic T-cells in 108 PTCL samples. TCR transcripts, including complementarity-determining region 3 (CDR3) sequences, were assessed. In normal T cells, the CDR3 sequences were extremely diverse, without any clonotype representing more than 2% of the overall TCR population. Dominant clones could be identified in 65 out of 76 PTCL cases (86%) with adequate TCR transcript expression. In monoclonal cases, the dominant clone varied between 11% and 99% of TCRβ transcripts. No unique Vα or Vβ usage was observed. Small T-cell clones were often observed in T- and NK-cell tumors in a percentage higher than observed in reactive conditions. γ chain expression was very low in tumors expressing TCRαβ, but its expression level was high and clonality was detected in a TCRγδ expressing tumor. NK cell lymphoma (NKCL) did not express significant levels of TCR Vβ or Vγ genes. RNA-seq is a useful tool for detecting and characterizing clonal TCR rearrangements in PTCL.

show abstract

References

2021

Flow Cytometry of Hematological Malignancies

View full text Add to dashboard Cite

Abnormal immunophenotype of the T‐cell‐receptor beta Chain in follicular‐helper T cells of angioimmunoblastic T‐cell lymphoma

Cited by 4 publications

References 18 publications

New preclinical models for angioimmunoblastic T-cell lymphoma: filling the GAP

New preclinical models for angioimmunoblastic T-cell lymphoma: filling the GAP

Assessment of T-cell receptor repertoire and clonal expansion in peripheral T-cell lymphoma using RNA-seq data

References

Contact Info

Product

Resources

About