The Association of STAT3 Activation with Interferon Therapy in Adult T-Cell Leukemia Lymphoma

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K17862
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: University of the Ryukyus
• Principal Investigator: MORICHIKA KAZUHO 琉球大学, 医学(系)研究科(研究院), 助教 (90793943)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: adult T cell lymphoma / STAT3 / immunohistochemistry / DNA sequencing / DLBCL

Outline of Final Research Achievements

Adult T-cell leukemia/lymphoma (ATLL) is a mature T-cell neoplasm, and is divided into 2 indolent (smoldering and chronic) and 2 aggressive (acute and lymphoma) clinical subtypes. We attempted to clarify the clinicopathological significance of JAK-STAT pathway. Clinical and morphological findings were reviewed in 116 cases with ATLL. The nuclear localizations of phosphorylated STAT3, 5, 6 (pSTAT) were analyzed by immunohistochemistry. Targeted sequencing was undertaken on the portion of STAT3 encoding the Src homology 2 domain. Both univariate and multivariate analysis revealed that pSTAT3 expression was significantly associated with better overall survival and progression-free survival in the smoldering type of ATLL, whereas STAT3 mutation was not related to a line of clinical outcome. Collectively, our data raises the possibility that pSTAT3 expression is a novel biomarker to predict better prognosis in the smoldering type of ATLL.

Free Research Field

造血器悪性腫瘍

Academic Significance and Societal Importance of the Research Achievements

上記に示す様にくすぶり型ATLにおける新たな予後因子を提唱した。さらに我々はびまん性大細胞型B細胞リンパ腫におけるpSTAT3の意義についても解析した。pSTAT3陽性GCB型は５年生存率が92%であるのに対し、pSTAT3陽性non-GCB型は45%と、Cell of OriginによりpSTAT3発現の臨床的意義が異なっていた。pSTAT3陽性GCB型は多変量解析でも予後良好因子として抽出された。遺伝子変異解析の結果、MYD88変異、EZH2変異、EBウイルス感染、BCL2/MYCの再構成といった予後不良とされる分子異常を伴う頻度が有意に低いことが予後良好と関連する背景として考えられた。