Emergence of Malignant T-Cell Intraclonal <i>CDR3</i> Variants in Mycosis Fungoides

Gleason, Laura; Cohen, Alexa; South, Andrew P.; Porcu, Pierluigi; Nikbakht, Neda

doi:10.1001/jamadermatol.2023.0826

Cited by 2 publications

(4 citation statements)

References 6 publications

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“…This has been exemplified by the discovery of intraclonal CDR3 variants, defined by one single base substitution in the constituent dominant TCRβ CDR3 sequences. The novel detection of intraclonal CDR3 variants was associated with changes in clinical and histopathologic behavior, including progression to tumor-stage MF, new-onset large cell transformation, and resistance to treatment ( 49 ). This observation demonstrates the importance of interrogating the CDR3 sequences throughout the course of disease.…”

Section: Utility Of Immunosequencing In Skinmentioning

confidence: 99%

“…As discussed above in section 3.3, the utility of HTS-TCR extends to identifying mutations that can arise in the dominant CDR3s. The existing study detected mutated versions of the malignant CDR3 clones that became dominant themselves ( 49 ). It would be interesting to further explore the prevalence and clinical relevance of mutated CDR3 clones that do not reach the level of dominance.…”

Section: Advancing Ctcl Research With Hts-tcrmentioning

confidence: 99%

“…It is not uncommon for multiple dominant sequences to be identified within CTCL skin biopsy specimens, and the clinical significance of detecting multiple clones is not yet clear ( 49 ). This is particularly challenging to interpret when three or more dominant sequences are detected.…”

Section: Challenges and Limitations Of Hts-tcr In Ctclmentioning

confidence: 99%

“…As previously mentioned in section 3.3, intraclonal CDR3 variants have been detected and described at our institution. The emergence of these mutated clones were associated with progression of disease as well as resistance to treatment ( 49 ). However, the clinical significance of intraclonal CDR3 variants needs to be studied further.…”

Section: Challenges and Limitations Of Hts-tcr In Ctclmentioning

confidence: 99%

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Immunosequencing applications in cutaneous T-cell lymphoma

Mandel,

Gleason,

Joffe

et al. 2023

Front. Immunol.

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Immunosequencing has emerged as a newer clinical test for assessment of T-cell clonality in the blood and skin of cutaneous T-cell lymphoma (CTCL) patients. Utilization of immunosequencing, also known as high-throughput sequencing of the T-cell receptor (HTS-TCR), enables identification and quantification of the precise genetic signature of dominant T-cell clones. Although immunosequencing is more sensitive than commonly used methods such as polymerase chain reaction (PCR) paired with capillary electrophoresis or flow cytometry, it remains underutilized for CTCL management. Nonetheless, incorporation of HTS-TCR in clinical practice offers distinct advantages compared to other molecular analyses that may improve diagnostic evaluation, prognostication, and disease monitoring in CTCL. The objective of this comprehensive review is to provide a thorough explanation of the application of immunosequencing in the context of CTCL. We describe the significance of T-cell clonality and the methods used to detect it, including a detailed comparison between PCR paired with capillary electrophoresis and HTS-TCR. The utilization of immunosequencing in the blood and skin of CTCL patients is discussed in depth, specifically outlining how HTS-TCR can assist in diagnosing CTCL, predicting outcomes, and tracking disease progression. Finally, we address the potential applications of immunosequencing in clinical management and research as well as the novel challenges it presents.

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Section: Utility Of Immunosequencing In Skinmentioning

confidence: 99%

Section: Advancing Ctcl Research With Hts-tcrmentioning

confidence: 99%

Section: Challenges and Limitations Of Hts-tcr In Ctclmentioning

confidence: 99%

Section: Challenges and Limitations Of Hts-tcr In Ctclmentioning

confidence: 99%

See 2 more Smart Citations

Immunosequencing applications in cutaneous T-cell lymphoma

Mandel,

Gleason,

Joffe

et al. 2023

Front. Immunol.

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Utility of T-cell immunosequencing in distinguishing mycosis fungoides progression from treatment related cutaneous adverse events

Bhatti,

Joffe,

Banner

et al. 2023

Front. Med.

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Cutaneous adverse events of both topical and systemic drugs in patients with mycosis fungoides (MF) present a diagnostic challenge as it is often difficult to distinguish drug associated rash from disease progression in the skin. Mogamulizumab and mechlorethamine gel are approved treatments for MF, both of which can cause treatment related cutaneous adverse events. It can often be challenging to distinguish mogamulizumab associated rash (MAR) and mechlorethamine gel associated hypersensitivity dermatitis from MF progression both clinically and histologically. High-throughput sequencing (HTS) of the T-cell receptor (TCR), also known as immunosequencing, can be used to assess T-cell clonality to support a diagnosis of MF. After identification of the malignant TCR clone at baseline, immunosequencing can track the established malignant TCR sequence and its frequency over time with high sensitivity. As a result, immunosequencing clone tracking can aid in distinguishing disease progression from treatment side effects. Here, we present a case series to demonstrate how monitoring of the malignant T-cell frequency by immunosequencing can aid in diagnosis of mogamulizumab and mechlorethamine gel cutaneous adverse events.

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Emergence of Malignant T-Cell Intraclonal CDR3 Variants in Mycosis Fungoides

Abstract: This case report describes 3 patients with mycosis fungoides with CDR3 variants.

Cited by 2 publications

References 6 publications

Immunosequencing applications in cutaneous T-cell lymphoma

Immunosequencing applications in cutaneous T-cell lymphoma

Utility of T-cell immunosequencing in distinguishing mycosis fungoides progression from treatment related cutaneous adverse events

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