|
Affiliation |
Faculty of Medicine College Hospital Department of Blood Medicine |
|
Related SDGs |
|
KAMIUNTEN Ayako
|
|
|
Papers 【 display / non-display 】
-
幣 光太郎, 亀田 拓郎, 内田 泰介, 上運天 綾子, 秋月 渓一, 久冨木 庸子, 池田 良磨, 宇都 倫史, 深谷 知宏, 三苫 修也, 佐藤 克明, 上平 雄大, 上野 浩晶, 山口 秀樹, 下田 和哉
Blood Neoplasia 2 ( 3 ) 100087 2025.8
Language：English Publishing type：Research paper (scientific journal) Publisher：Elsevier BV
Interferon-α (IFN-α) exhibits antiviral and antiproliferative effects on normal and neoplastic cells. Intracellular signaling of IFN-α is mediated by tyrosine kinase 2 (TYK2) and janus kinase 1 (JAK1), followed by signal transducers and activators of transcription (STATs). TYK2 is redundant for the antiviral effect of IFN-α; however, the requirements for antiproliferative effects are unknown. We assessed the role of TYK2 in the effects of IFN-α in myeloproliferative neoplasm (MPN) model mice. Jak2V617F transgenic mice develop MPNs resembling human primary myelofibrosis, and ropeginterferon-α-2b ameliorated their features. However, these IFN-α effects were absent in Jak2V617F;Tyk2−/− mice. In mixed wild-type (WT)/Jak2V617F chimeric mice, IFN-α treatment induces Jak2V617F hematopoietic stem cells (HSCs) to enter the cell cycle and skew their differentiation into the megakaryocyte lineage, decreasing the number of Jak2V617F HSCs. The effects of IFN-α on Jak2V617F HSCs were not observed in mixed WT/Jak2V617F;Tyk2−/− mice, indicating that TYK2 is essential for the effects of IFN-α on both Jak2V617F progenitors and HSCs. The mechanism of IFN-α in Jak2V617F HSCs and progenitors differed: genes regulating the cell cycle were enriched in IFN-α–stimulated Jak2V617F HSCs, but not in Jak2V617F progenitors; genes regulating antiproliferation were enriched in IFN-α–stimulated Jak2V617F progenitors but not in Jak2V617F HSCs. The major IFN-α signaling molecule activated by JAKs is STAT1, which is essential for the antiviral effect. Most effects of IFN-α on Jak2V617F cells were preserved in Jak2V617F;Stat1−/− mice but to a moderate degree compared with Jak2V617F mice. Our study reveals essential roles of TYK2 for the preferential suppressive effect of IFN-α on Jak2V617F progenitors and HSCs.
-
Effects of tucidinostat in adult T-cell leukemia/lymphoma in clinical practice Reviewed
Kamiunten A., Kameda T., Sekine M., Kawano H., Toyama T., Akizuki K., Kawano N., Maeda K., Sato S., Takeuchi M., Ishizaki J., Nagamine K., Kuroki A., Ikeda R., Matsumoto K., Karasawa M., Tahira Y., Uchida T., Shimoda H., Hidaka T., Yamashita K., Yamaguchi H., Kubuki Y., Shimoda K., Shide K.
International Journal of Hematology 122 ( 1 ) 83 - 92 2025
Authorship：Lead author Publishing type：Research paper (scientific journal) Publisher：International Journal of Hematology
Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell malignancy with a poor prognosis. We conducted a retrospective study across six institutions in Miyazaki Prefecture, Japan, to assess the efficacy of tucidinostat in patients with relapsed/refractory ATL who had not undergone transplantation. Between October 2021 and July 2023, 24 patients aged 41 to 88 years (median, 73.4 years) who had undergone prior therapies, including intensive chemotherapy (79.2%) and mogamulizumab immunotherapy (79.2%), received tucidinostat. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were evaluated as key outcomes. ORR and DCR reached 54.2% and 91.7%, respectively. The median PFS was 3.95 months, and OS was 8.04 months, which were not inferior to the results of a phase IIb study. The influential factors for PFS were age ≥ 75 years and high soluble IL-2 receptor (sIL-2R) levels above 5000 U/mL at the start of treatment. Favorable patients without these factors achieved a PFS of 11.4 months. Treatment-related adverse events were mainly hematologic but were managed over the course of treatment. Our findings indicate that tucidinostat provides survival benefits in patients with relapsed/refractory ATL in clinical practice and highlight key clinical factors for better outcomes.
-
Impaired humoral immunity following COVID-19 vaccination in HTLV-1 carriers Reviewed
Kameda T., Utsunomiya A., Otsuka N., Kubuki Y., Uchida T., Shide K., Kamiunten A., Nakano N., Tokunaga M., Miyazono T., Ito Y., Yonekura K., Kawakita T., Akizuki K., Tahira Y., Karasawa M., Hidaka T., Konagata A., Taniguchi N., Nagatomo Y., Kogo F., Shimizu K., Ueno H., Ishizaki J., Takahashi N., Ikei Y., Hidaka M., Yamaguchi H., Shimoda K.
BMC Infectious Diseases 24 ( 1 ) 2024.12
Publishing type：Research paper (scientific journal) Publisher：BMC Infectious Diseases
Background: Whether human T-lymphotropic virus type 1 (HTLV-1) carriers can develop sufficient humoral immunity after coronavirus disease 2019 (COVID-19) vaccination is unknown. Methods: To investigate humoral immunity after COVID-19 vaccination in HTLV-1 carriers, a multicenter, prospective observational cohort study was conducted at five institutions in southwestern Japan, an endemic area for HTLV-1. HTLV-1 carriers and HTLV-1-negative controls were enrolled for this study from January to December 2022. During this period, the third dose of the COVID-19 vaccine was actively administered. HTLV-1 carriers were enrolled during outpatient visits, while HTLV-1-negative controls included health care workers and patients treated by participating institutions for diabetes, hypertension, or dyslipidemia. The main outcome was the effect of HTLV-1 infection on the plasma anti-COVID-19 spike IgG (IgG-S) titers after the third dose, assessed by multivariate linear regression with other clinical factors. Results: We analyzed 181 cases (90 HTLV-1 carriers, 91 HTLV-1-negative controls) after receiving the third dose. HTLV-1 carriers were older (median age 67.0 vs. 45.0 years, p < 0.001) and more frequently had diabetes, hypertension, or dyslipidemia than did HTLV-1-negative controls (60.0% vs. 27.5%, p < 0.001). After the third dose, the IgG-S titers decreased over time in both carriers and controls. Multivariate linear regression in the entire cohort showed that time since the third dose, age, and HTLV-1 infection negatively influenced IgG-S titers. After adjusting for confounders such as age, or presence of diabetes, hypertension, or dyslipidemia between carriers and controls using the overlap weighting propensity score method, and performing weighted regression analysis in the entire cohort, both time since the third dose and HTLV-1 infection negatively influenced IgG-S titers. Conclusions: The humoral immunity after the third vaccination dose is impaired in HTLV-1 carriers; thus, customized vaccination schedules may be necessary for them.
-
Kitamura A., Yanagi S., Shide K., Sato Y., Kamiunten A., Yamanari Y., Kitamura A., Sumiyoshi M., Oda Y., Tsubouchi H., Shimoda K., Miyazaki T.
American Journal of Case Reports 25 2024
Publishing type：Research paper (scientific journal) Publisher：American Journal of Case Reports
Patient: Male, 32-year-old Final Diagnosis: B-acute lymphoblastic leukemia Symptoms: Dyspnea • face swelling Clinical Procedure: — Specialty: Oncology Objective: Unknown etiology Background: Fibrosing mediastinitis (FM) is a rare, fibroproliferative disorder within the mediastinum. It is extremely rare for hematologic malignancies to develop as FM. Case Report: A 32-year-old Japanese man with a 1-month history of headache and 2-week history of facial swelling underwent chest computed tomography (CT); a diffuse mass-like lesion was revealed in the anterior mediastinum with severe stenosis of vital mediastinal organs. After a surgical biopsy, an initial diagnosis of idiopathic FM was made. The FM lesions responded mildly to corticosteroids but recurred repeatedly. Sixteen months after the treatment initiation, blasts appeared in the peripheral blood (PB), and the patient was diagnosed with B-acute lymphoblastic leukemia/lymphoblastic lymphoma (B-ALL/LBL). Chemotherapy led to complete remission of the B-ALL/LBL and almost complete disappearance of FM-like lesions. Immunohistochemistry of the mediastinal biopsy specimen taken before the blasts’ appearance in PB demonstrated a CD34/CD7/terminal deoxynucleotidyl transferase-positive population, an identical pattern of expression common to the blasts in the patient’s PB and bone marrow. Conclusions: This is the first case report of B-ALL/LBL presenting as FM. This case underscores the importance of considering the possibility of latent hematologic malignancy even in the absence of new symptoms other than those caused by FM lesions for a long period of time. This is the first demonstration that leukemia cells may be present in the FM lesions from the initial stage of disease onset. Even if a diagnosis of idiopathic FM is confirmed, continued suspicion of the presence of hematologic malignancy is vital for improving patient outcomes.
DOI： 10.12659/AJCR.945804
-
Integrated genetic and clinical prognostic factors for aggressive adult T-cell leukemia/lymphoma
Kameda T., Kataoka K., Kamiunten A., Hidaka M., Miyoshi H., Nakano N., Nosaka K., Yoshimitsu M., Yasunaga J.I., Kogure Y., Shide K., Miyahara M., Sakamoto T., Akizuki K., Hidaka T., Kubuki Y., Koya J., Kawano N., Yamashita K., Kawano H., Toyama T., Maeda K., Marutsuka K., Imaizumi Y., Kato K., Sugio T., Tokunaga M., Tashiro Y., Takaori-Kondo A., Miyazaki Y., Akashi K., Ishitsuka K., Matsuoka M., Ohshima K., Watanabe T., Kitanaka A., Utsunomiya A., Ogawa S., Shimoda K.
Haematologica 108 ( 8 ) 2178 - 2191 2023.8
Publishing type：Research paper (scientific journal) Publisher：Haematologica
The prognosis of aggressive adult T-cell leukemia/lymphoma (ATL) is poor, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment. In order to identify favorable prognostic patients after intensive chemotherapy, and who therefore might not require upfront allo-HSCT, we aimed to improve risk stratification of aggressive ATL patients aged <70 years. The clinical risk factors and genetic mutations were incorporated into risk modeling for overall survival (OS). We generated the m7-ATLPI, a clinicogenetic risk model for OS, that included the ATL prognostic index (PI) (ATL-PI) risk category, and non-silent mutations in seven genes, namely TP53, IRF4, RHOA, PRKCB, CARD11, CCR7, and GATA3. In the training cohort of 99 patients, the m7-ATLPI identified a low-, intermediate-, and high-risk group with 2-year OS of 100%, 43%, and 19%, respectively (hazard ratio [HR] =5.46; P<0.0001). The m7-ATLPI achieved superior risk stratification compared to the current ATL-PI (C-index 0.92 vs. 0.85, respectively). In the validation cohort of 84 patients, the m7-ATLPI defined low-, intermediate-, and high-risk groups with a 2-year OS of 81%, 30%, and 0%, respectively (HR=2.33; P=0.0094), and the model again outperformed the ATL-PI (C-index 0.72 vs. 0.70, respectively). The simplified m7-ATLPI, which is easier to use in clinical practice, achieved superior risk stratification compared to the ATLPI, as did the original m7-ATLPI; the simplified version was calculated by summing the following: high-risk ATL-PI category (+10), low-risk ATL-PI category (−4), and non-silent mutations in TP53 (+4), IRF4 (+3), RHOA (+1), PRKCB (+1), CARD11 (+0.5), CCR7 (−2), and GATA3 (−3).
Presentations 【 display / non-display 】
-
Clinical Outcomes of Valemetostat Therapy for Relapsed/Refractory Adult T-cell Leukemia-Lymphoma (ATL) in Miyazaki Prefecture
Ayako Kamiunten
2024.11.10
Event date： 2024.11.8 - 2024.11.10
Language：Japanese Presentation type：Oral presentation (general)
-
Retrospective analysis of hematopoietic stem cell transplantation for ATL in University of Miyazaki
上運天 綾子
第86回日本血液学会学術集会 2024.10.13
Event date： 2024.10.11 - 2024.10.13
Language：Japanese Presentation type：Poster presentation
-
Clinical Outcomes of Tucidinostat Therapy for Relapsed/Refractory Adult T-cell Leukemia-Lymphoma (ATL) in Clinical Practice
Ayako Kamiunten
2023.11.12
Event date： 2023.11.10 - 2023.11.12
Language：Japanese Presentation type：Oral presentation (general)
-
Loss of EZH2 does not affect the severity of murine myeloproliferative neoplasms with CALR mutation
上運天 綾子
第83回日本血液学会学術集会 2021.9.24
Event date： 2021.9.23 - 2021.9.25
Language：Japanese Presentation type：Oral presentation (general)
-
Development of MALT1 inhibitor and its effect on ATL
上運天 綾子
第82回日本血液学会学術集会 2020.10.10
Event date： 2020.10.10 - 2020.11.8
Language：Japanese Presentation type：Oral presentation (general)
Grant-in-Aid for Scientific Research 【 display / non-display 】
-
骨髄増殖性腫瘍におけるエピゲノム異常の役割
Grant number：19K17834 2019.04 - 2022.03
科学研究費補助金 若手研究
Authorship：Principal investigator