CCR4 mutations associated with superior outcome of adult T-cell leukemia/lymphoma under mogamulizumab treatment

Sakamoto, Yuma; Ishida, Takashi; Awata, Masaki; Murase, Takayuki; Yonekura, Kentaro; Tashiro, Yoshihiko; Tokunaga, Masahito; Utsunomiya, Atae; Ito, Asahi; Kusumoto, Shigeru; Iida, Shinsuke; Ueda, Ryuzo; Inagaki, Hiroshi

doi:10.1182/blood-2018-02-835991

Cited by 73 publications

(68 citation statements)

References 20 publications

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“…CCR4 mutation was found to predict a better response to the anti-CCR4 antibody mogamulizumab, suggesting the possibility of this mutation as a biomarker. 40 In addition, patients with Hodgkin lymphoma harboring PD-L1 genetic alteration exhibit superior outcomes following PD-1 blockade therapy, although this alteration is associated with shorter survival after conventional chemotherapy. 41 , 42 Thus, PD-L1 amplification and 3′-UTR truncation may function as predictive biomarkers for immune checkpoint blockade therapy in ATL.…”

Section: Genetic Alterations As Therapeutic Targets For Atlmentioning

confidence: 99%

Clinical application of genomic aberrations in adult T-cell leukemia/lymphoma

Kataoka¹,

Koya²

2020

J Clin Exp Hematopathol

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Adult T-cell leukemia/lymphoma (ATL) is an aggressive peripheral T-cell malignancy with a markedly poor prognosis. The low prevalence of ATL among human T-cell leukemia virus type-1 (HTLV-1) carriers and the long latency period before ATL onset suggest that additional genetic lesions are required for ATL leukemogenesis. Recently, a large-scale genetic analysis clarified the entire picture of genetic alterations, identified a number of novel driver genes, and delineated their characteristics. Frequent alterations are observed in the molecules belonging to T-cell receptor/NF-κB signaling and other T-cell-related pathways. A notable feature of the ATL genome is the predominance of gain-of-function alterations, including activating mutations in PLCG1 , PRKCB , and CARD11 . As many as one-fourth of all ATL cases harbor structural variations disrupting the 3′-untranslated region of the PD-L1 gene, leading to immune evasion of tumor cells. The frequency and pattern of these somatic alterations differ among clinical subtypes. Aggressive subtypes are associated with an increased burden of genetic alterations, and higher frequencies of TP53 and IRF4 mutations, PD-L1 amplifications, and CDKN2A deletions than indolent subtypes. In contrast, STAT3 mutations are more characteristic of indolent ATL. Furthermore, these subtypes are further classified into molecularly distinct subsets with a different prognosis by genetic alterations. We present an overview of the current understanding of somatic alterations in ATL, with specific focus on their utility in clinical settings. Furthermore, we highlight their genetic features by exploring their similarities and differences among peripheral T-cell lymphomas.

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Section: Genetic Alterations As Therapeutic Targets For Atlmentioning

confidence: 99%

Clinical application of genomic aberrations in adult T-cell leukemia/lymphoma

Kataoka¹,

Koya²

2020

J Clin Exp Hematopathol

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“…3 In a recent study, CCR4 gain-of-function mutations were observed in 32.8% of 116 patients from Japan and were found to be prognostic of treatment response with a 5-year overall survival difference of 80% in the group with CCR4 gain-of-function mutations versus 24.7% in the group without these mutations. 4 In a group of 53 predominantly North American patients with ATLL, 14 (26%) had a CCR4 gain-of-function mutation. 5 While genomic analyses have not yet been reported for this trial, this finding underlies the importance of performing such studies in phase II trials.…”

Section: Identifying Potential Factors Of Variable Response To Mogamumentioning

confidence: 99%

Identifying potential factors of variable response to mogamulizumab in adult T-cell leukemia/lymphoma between Japanese and other populations

Janakiram

Miljković

2019

Haematologica

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“…An appropriate use of mogamulizumab for patients with ATL who plan to undergo allo-HCT is now developing in Japan [44]. In patients with ATL who have CCR4 mutations of ATL cells, mogamulizumab therapy confers better OS compared to that in patients without CCR4 mutations [45].…”

Section: Current Treatmentmentioning

confidence: 99%

Sensitive Photodynamic Detection of Adult T-cell Leukemia/Lymphoma and Specific Leukemic Cell Death Induced by Photodynamic Therapy: Current Status in Hematopoietic Malignancies

Oka

Matsuoka

Utsunomiya

2020

Cancers

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Adult T-cell leukemia/lymphoma (ATL), an aggressive type of T-cell malignancy, is caused by the human T-cell leukemia virus type I (HTLV-1) infections. The outcomes, following therapeutic interventions for ATL, have not been satisfactory. Photodynamic therapy (PDT) exerts selective cytotoxic activity against malignant cells, as it is considered a minimally invasive therapeutic procedure. In PDT, photosensitizing agent administration is followed by irradiation at an absorbance wavelength of the sensitizer in the presence of oxygen, with ultimate direct tumor cell death, microvasculature injury, and induced local inflammatory reaction. This review provides an overview of the present status and state-of-the-art ATL treatments. It also focuses on the photodynamic detection (PDD) of hematopoietic malignancies and the recent progress of 5-Aminolevulinic acid (ALA)-PDT/PDD, which can efficiently induce ATL leukemic cell-specific death with minor influence on normal lymphocytes. Further consideration of the ALA-PDT/PDD system along with the circulatory system regarding the clinical application in ATL and others will be discussed. ALA-PDT/PDD can be promising as a novel treatment modality that overcomes unmet medical needs with the optimization of PDT parameters to increase the effectiveness of the tumor-killing activity and enhance the innate and adaptive anti-tumor immune responses by the optimized immunogenic cell death.

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CCR4 mutations associated with superior outcome of adult T-cell leukemia/lymphoma under mogamulizumab treatment

Cited by 73 publications

References 20 publications

Clinical application of genomic aberrations in adult T-cell leukemia/lymphoma

Clinical application of genomic aberrations in adult T-cell leukemia/lymphoma

Identifying potential factors of variable response to mogamulizumab in adult T-cell leukemia/lymphoma between Japanese and other populations

Sensitive Photodynamic Detection of Adult T-cell Leukemia/Lymphoma and Specific Leukemic Cell Death Induced by Photodynamic Therapy: Current Status in Hematopoietic Malignancies

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