Epigenetic focus on angioimmunoblastic T-cell lymphoma: pathogenesis and treatment

Tari, Gamze; Lemonnier, François; Morschhauser, Franck

doi:10.1097/cco.0000000000000773

Cited by 10 publications

(9 citation statements)

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“…35 Histone deacetylase inhibitors (HDACi) have shown efficacy in the treatment of AITL and presented promising results. 36 Approximately 47% of AITL patients carry a mutation in TET2, which encodes a protein that is regulated by acetylation. 34 HDAC1 and HDAC2 mediate deacetylation of TET2, leading to its ubiquitination and proteasome-mediated degradation.…”

Section: Discussionmentioning

confidence: 99%

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Chidamide plus prednisone, etoposide, and thalidomide for untreated angioimmunoblastic T‐cell lymphoma in a Chinese population: A multicenter phase II trial

et al. 2022

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Angioimmunoblastic T-cell lymphoma (AITL) is a common type of peripheral T-cell lymphoma (PTCL) with a poor prognosis, and an effective first-line therapy is lacking.Chidamide is a selective histone deacetylase inhibitor and has been approved by the China Food and Drug Administration for relapsed or refractory PTCL. We conducted a multicenter phase II clinical trial combining chidamide with prednisone, etoposide, and thalidomide (CPET regimen) for a total of eight cycles in untreated AITL patients in China. The primary objectives were the overall response rate (ORR) and complete remission (CR) rate after eight cycles of the CPET regimen. The secondary endpoints were progression-free survival (PFS) and safety. Of the 71 enrolled patients, 51 completed the eight cycles of the CPET regimen. The ORR and CR of the 51 patients were 90.2 and 54.9%, respectively. After a median follow-up of 11.4 months (95% confidence interval[CI], 9.9-17.0), the median PFS of the 51 patients was 42.6 months (95% CI, 27.7-not reached) and the median overall survival (OS) was not reached. The 2-year PFS rate and OS rate were 66.5 and 82.2%, respectively. Sixty-eight patients received at least one cycle of CPET regimen and were included as the safety assessment population. The most common grade 3/4 adverse event was neutropenia (n = 22, 32.3%). Twelve patients showed treatment-related infections and recovered from antibiotic therapy; the other adverse events were mostly mild and reversible. The oral CPET regimen is an effective, tolerable, and economical choice for untreated AITL in a Chinese population. This trial was registered in www.clinicaltrials.gov as NCT03273452. | INTRODUCTIONAngioimmunoblastic T-cell lymphoma (AITL) is a mature T-cell lymphoma as defined by the World Health Organization (WHO) 2016 Classification. 1 Globally, AITL accounts for 1-2% of non-Hodgkin lymphomas and 15-20% of peripheral T-cell lymphoma (PTCL), and AITL is the second most common PTCL after PTCL not otherwise specified. 2 AITL accounted for 1.6% of non-Hodgkin lymphomas and

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Section: Discussionmentioning

confidence: 99%

“…Histone deacetylases (HDACs) act as epigenetic modifiers that regulate signaling pathways via the deacetylation of histone proteins and non‐histone proteins 35 . Histone deacetylase inhibitors (HDACi) have shown efficacy in the treatment of AITL and presented promising results 36 …”

Section: Discussionmentioning

confidence: 99%

Chidamide plus prednisone, etoposide, and thalidomide for untreated angioimmunoblastic T‐cell lymphoma in a Chinese population: A multicenter phase II trial

et al. 2022

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“…We diagnosed AITL in the BM samples from 41/49 (83.7%) patients studied for FCI. AITL is a well-established and relatively common subtype among the group of T-NHLs (26,(76)(77)(78)(79)(80)(81). However, it is challenging to diagnose due to the lack of a unique histopathological pattern and its relatively low tumor burden in the background of abundant inflammatory cells (26,77,79,81,82).…”

Section: Discussionmentioning

confidence: 99%

Critical Role of Flow Cytometric Immunophenotyping in the Diagnosis, Subtyping, and Staging of T-Cell/NK-Cell Non-Hodgkin’s Lymphoma in Real-World Practice: A Study of 232 Cases From a Tertiary Cancer Center in India

et al. 2022

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BackgroundT-cell/NK-cell non-Hodgkin’s lymphoma (T/NK-NHL) is an uncommon heterogeneous group of diseases. The current classification of T/NK-NHL is mainly based on histopathology and immunohistochemistry. In practice, however, the lack of unique histopathological patterns, overlapping cytomorphology, immunophenotypic complexity, inadequate panels, and diverse clinical presentations pose a great challenge. Flow cytometric immunophenotyping (FCI) is a gold standard for the diagnosis, subtyping, and monitoring of many hematological neoplasms. However, studies emphasizing the role of FCI in the diagnosis and staging of T/NK-NHL in real-world practice are scarce.MethodsWe included T-cell non-Hodgkin’s lymphoma (T-NHL) patients evaluated for the diagnosis and/or staging of T/NK-NHL using FCI between 2014 and 2020. We studied the utility of FCI in the diagnosis and subtyping of T/NK-NHL and correlated the FCI findings with the results of histopathology/immunohistochemistry. For correlation purposes, patients were categorized under definitive diagnosis and subtyping, inadequate subtyping, inadequate diagnosis, and misdiagnosis based on the findings of each technique.ResultsA total of 232 patients were diagnosed with T/NK-NHL. FCI findings provided definitive diagnoses in 198 patients and subtyping in 187/198 (95.45%) patients. The correlation between FCI and histopathological/immunohistochemistry results (n = 150) demonstrated an agreement on the diagnosis and subtyping in 69/150 (46%) patients. Of the remaining cases, the diagnosis and subtyping were inadequate in 64/150 (42.7%), and 14/150 (9.33%) were misdiagnosed on histopathology/immunohistochemistry results. FCI provided definitive diagnosis and subtyping in 51/64 (79.7%) patients. Among these, 13 patients diagnosed with peripheral T-cell lymphoma not-otherwise-specified were reclassified (angioimmunoblastic T-cell lymphoma (AITL)-11 and prolymphocytic leukemia-2) on FCI. It corrected the diagnosis in 14 patients that were misdiagnosed (6 B-cell NHL (B-NHL), 3 Hodgkin’s lymphoma, 1 acute leukemia, and 1 subcutaneous panniculitis-like T-cell lymphoma) and misclassified (3 T-NHL) on histopathological results. AITL was the commonest T-NHL misclassified on histopathological results. FCI also confirmed the definite involvement in 7/83 (8.4%) and 27/83 (32.5%) bone marrow (BM) samples reported as suspicious and uninvolved, respectively, on histopathological evaluation.ConclusionAITL was the most frequently diagnosed T/NK-NHL in this study. FCI provided a distinct advantage in detecting BM involvement by T/NK-NHL, especially in patients with low-level involvement. Overall, our study concluded that FCI plays a critical role in the diagnosis, subtyping, and staging of T/NK-NHL in real-world practice.

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“…According to the 2022 NCCN guidelines, anthracycline-based chemotherapy regimens [e.g., CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), CHOP + etoposide (CHOEP), or dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin)] are the most commonly used first-line therapy regimens, although with a high failure rate and frequent relapse in PTCL. Additionally, epigenetic drugs have been applied in clinical trials ( Table 2 ) and recommended as second-line therapy by NCCN clinical practice guidelines [ 70 ], providing new research directions to promote promising clinical outcomes as a focus of research in PTCL [ 71 ].…”

Section: New Drugs Targeting Tet2 For Treatment Of...mentioning

confidence: 99%

Targeting TET2 as a Therapeutic Approach for Angioimmunoblastic T Cell Lymphoma

Zhang

et al. 2022

Cancers

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Angioimmunoblastic T-cell lymphoma (AITL), a type of malignant lymphoma with unique genomic aberrations, significant clinicopathological features, and poor prognosis, is characterized by immune system dysregulation. Recent sequencing studies have identified recurrent mutations and interactions in tet methylcytosine dioxygenase 2 (TET2), ras homology family member A (RHOA), DNA methyltransferase 3 alpha (DNMT3A), and mitochondrial isocitrate dehydrogenase II (IDH2). Notably, since B-cell lymphomas are frequently observed along with AITL, this review first summarizes its controversial mechanisms based on traditional and recent views. Epigenetic regulation represented by TET2 plays an increasingly important role in understanding the multi-step and multi-lineage tumorigenesis of AITL, providing new research directions and treatment strategies for patients with AITL. Here, we review the latest advances in our understanding of AITL and highlight relevant issues that have yet to be addressed in clinical practice.

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Epigenetic focus on angioimmunoblastic T-cell lymphoma: pathogenesis and treatment

Cited by 10 publications

References 51 publications

Chidamide plus prednisone, etoposide, and thalidomide for untreated angioimmunoblastic T‐cell lymphoma in a Chinese population: A multicenter phase II trial

Chidamide plus prednisone, etoposide, and thalidomide for untreated angioimmunoblastic T‐cell lymphoma in a Chinese population: A multicenter phase II trial

Critical Role of Flow Cytometric Immunophenotyping in the Diagnosis, Subtyping, and Staging of T-Cell/NK-Cell Non-Hodgkin’s Lymphoma in Real-World Practice: A Study of 232 Cases From a Tertiary Cancer Center in India

Targeting TET2 as a Therapeutic Approach for Angioimmunoblastic T Cell Lymphoma

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