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Title :Phosphorylated STAT3 expression predicts better prognosis in smoldering type of adult T‐cell leukemia/lymphoma
Authors :Morichika, Kazuho
Karube, Kennosuke
Kayo, Hirona
Uchino, Shuta
Nishi, Yukiko
Nakachi, Sawako
Okamoto, Shiki
Morishima, Satoko
Ohshiro, Kazuiku
Nakazato, Iwao
Fukushima, Takuya
Masuzaki, Hiroaki
Issue Date :Sep-2019
Abstract :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. Based on previous integrated molecular analyses suggesting the importance of the JAK‐STAT pathway in ATLL, we attempted to clarify the clinicopathological significance of this pathway. Clinical and morphological findings were reviewed in 116 cases with ATLL. The nuclear localizations of phosphorylated STAT3 (pSTAT3), pSTAT5, and pSTAT6 were analyzed by immunohistochemistry. Targeted sequencing was undertaken on the portion of STAT3 encoding the Src homology 2 domain. Expression of pSTAT3 was observed in 43% (50/116) of ATLL cases, whereas pSTAT5 and pSTAT6 were largely undetected. Cases with the lymphoma type showed significantly less frequent pSTAT3 expression (8/45, 18%) than those with the other subtypes (41/66, 62%; P < .001). STAT3 mutations were detected in 36% (10/28) and 19% (12/64) of cases with the smoldering and aggressive types of ATLL, respectively. The correlation between STAT3 mutation and pSTAT3 expression was not significant (P = .07). 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 show that only the lymphoma type showed a low prevalence of tumor cells positive for pSTAT3 expression, and raises the possibility that pSTAT3 expression is a novel biomarker to predict better prognosis in the smoldering type of ATLL.
URL :https://doi.org/10.1111/cas.14114
Type Local :雑誌掲載論文
ISSN :1349-7006
1347-9032
Publisher :Wiley
URI :http://hdl.handle.net/20.500.12000/47231
Citation :Cancer Science Vol.110 no.9 p.2982 -2991
Appears in Collections:Peer-reviewed Journal Articles (Faculty of Medicine)

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