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Wilms Tumor 1 Expression at Diagnosis Correlates With Genetic Abnormalities and Polymorphism But Is Not Independently Prognostic in Acute Myelogenous Leukemia : A Hokkaido Leukemia Net Study

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Title: Wilms Tumor 1 Expression at Diagnosis Correlates With Genetic Abnormalities and Polymorphism But Is Not Independently Prognostic in Acute Myelogenous Leukemia : A Hokkaido Leukemia Net Study
Authors: Hidaka, Daisuke Browse this author
Onozawa, Masahiro Browse this author →KAKEN DB
Hashiguchi, Junichi Browse this author
Miyashita, Naohiro Browse this author
Kasahara, Kohei Browse this author
Fujisawa, Shinichi Browse this author
Hayase, Eiko Browse this author
Okada, Kohei Browse this author
Shiratori, Souichi Browse this author →KAKEN DB
Goto, Hideki Browse this author
Sugita, Junichi Browse this author
Nakagawa, Masao Browse this author
Hashimoto, Daigo Browse this author
Kahata, Kaoru Browse this author
Endo, Tomoyuki Browse this author
Yamamoto, Satoshi Browse this author
Tsutsumi, Yutaka Browse this author
Haseyama, Yoshihito Browse this author
Nagashima, Takahiro Browse this author
Mori, Akio Browse this author
Ota, Shuichi Browse this author
Sakai, Hajime Browse this author
Ishihara, Toshimichi Browse this author
Imai, Kiyotoshi Browse this author
Miyagishima, Takuto Browse this author
Kakinoki, Yasutaka Browse this author
Kurosawa, Mitsutoshi Browse this author
Kobayashi, Hajime Browse this author
Iwasaki, Hiroshi Browse this author
Shimizu, Chikara Browse this author →KAKEN DB
Kondo, Takeshi Browse this author →KAKEN DB
Teshima, Takanori Browse this author →KAKEN DB
Keywords: WT1
prognostic stratification
Hokkaido Leukemia Net (HLN)
North Japan Hematology Study Group (NJHSG)
Issue Date: Nov-2018
Publisher: Elsevier
Journal Title: Clinical Lymphoma, Myeloma and Leukemia
Volume: 18
Issue: 11
Start Page: e469
End Page: e479
Publisher DOI: 10.1016/j.clml.2018.07.291
Abstract: The association between Wilms tumor 1 (WT1) expression, genetic abnormalities and homozygous single polymorphism (SNP) in WT1 gene was evaluated in 252 acute myelogenous leukemia (AML) patients. WT1 expression correlated with prognostic genetic abnormalities. Homozygous WT1 SNP rs16754 was associated with lower expression of WT1. WT1 expression had no prognostic impact in any cytogenetic group or SNP status. Background: The prognostic impact of WT1 expression at diagnosis of acute myelogenous leukemia (AML) has been controversial. The aim of this study was to determine the correlations of WT1 expression at diagnosis of AML with established prognostic alterations. Patients and Methods: We analyzed diagnostic bone marrow samples from 252 patients. WT1 expression, SNP in WT1 gene (rs16754), and Flt3-ITD mutation were analyzed for all patients. NPM1 mutation and CEBPA double mutation were analyzed for cytogenetically normal (CN)-AML. KIT mutation was analyzed for core-binding factor (CBF)-AML. Results: Within the cytogenetically favorable prognosis group, WT1 expression in AML with inv(16) or t(15;17) was significantly higher than that in AML with t(8;21). In cases with CN-AML, Flt3-ITD and NPM1 mutations were both correlated with higher expression of WT1, whereas CEBPA double mutation was related to lower WT1 expression. The existence of both Flt3- ITD and NPM1 mutations showed synergistically higher expression of WT1 in CN-AML. SNP in WT1 gene (rs16754) was significantly associated with lower expression of WT1. WT1 levels were not prognostic factors in the total cohort, in any cytogenetic group nor SNP status. Conclusion: Since WT1 expression correlated to known prognostic factors, the prognostic impact of WT1 levels might be misunderstood depending on the distribution of collaborative mutations in each cohort. We conclude that the prognostic significance of WT1 at diagnosis of AML is weak compared to other established prognostic factors.
Rights: © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license
Type: article (author version)
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 小野澤 真弘

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