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Multicenter Study
. 2025 Jan;104(1):275-284.
doi: 10.1007/s00277-025-06227-y. Epub 2025 Feb 8.

Prognostic impact of TET2 mutations in patients with acute myeloid leukemia: HM-SCREEN-Japan 01 and 02 study

Satoshi Iyama  1 , SungGi Chi  2 , Masashi Idogawa  3 , Takayuki Ikezoe  4 , Kentaro Fukushima  5 , Yoshikazu Utsu  6 , Junya Kanda  7 , Goichi Yoshimoto  8 , Takahiro Kobayashi  9 , Naoko Hosono  10 , Takahiro Yamauchi  10 , Takeshi Kondo  11 , Yukinori Nakamura  12 , Kensuke Kojima  13 , Chikashi Yoshida  14 , Akihiko Gotoh  15 , Kazuhito Yamamoto  16 , Junya Kuroda  17 , Kenji Ishitsuka  18 , Emiko Sakaida  19 , Hiroto Horiguchi  20 , Kohichi Takada  21 , Hirofumi Ohnishi  22 , Masayoshi Kobune  20 , Yosuke Minami  2
Affiliations
Multicenter Study

Prognostic impact of TET2 mutations in patients with acute myeloid leukemia: HM-SCREEN-Japan 01 and 02 study

Satoshi Iyama et al. Ann Hematol. 2025 Jan.

Abstract

Ten-eleven translocation-2 (TET2) gene mutations are observed in 12-20% of adult patients with acute myeloid leukemia (AML). The prognostic impact of TET2 mutations in patients with AML and myelodysplastic syndromes has been reported in several studies; however, their results remain controversial. Therefore, we aimed to analyze the prevalence and significance of TET2 mutations in patients with AML. Data were obtained from 331 patients with AML according to the Hematologic Malignancies-SCREEN-Japan 01 and 02 studies, which were prospective multicenter genomic profiling analyses. We found a distinct type of TET2 mutations, with a particularly detrimental prognosis in the patients. Thirty-five patients with TET2 'significant' mutations were identified (26 with frameshift mutations and nine with nonsense mutations). The proportion of patients with TET2 mutations was 31.7% (10.6% and 21.1% in the TET2 significant and non-significant mutation groups). The TET2 significant mutation group had a shorter OS than the TET2 non-significant mutation or wild-type TET2 group (median: 15.9 vs. 35.0 vs. 25.9 months). Regarding the response to chemotherapy according to TET2 status, the complete response (CR) or CR with incomplete count recovery rate was 37.1% in the TET2 significant mutation group and 46.6% in the non-significant mutation or wild-type group. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) improved patient prognosis in the TET2 non-significant mutation or wild-type TET2 group; however, allo-HSCT did not affect prognosis in the TET2 significant mutation group. This study indicates that certain TET2 mutations in patients with AML may have detrimental effects.

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Conflict of interest statement

Declarations. Non-financial interest: Not applicable. Competing interests: S.I. has received research funding from MSD, Otsuka, JCR pharma, Chugai pharmaceutical, Kyowa Kirin, Novartis; has received honoraria from Alexion Pharmaceuticals, Astellas, Nippon Shinyaku, Novartis, Otsuka, Sanofi, SymBio Pharmaceuticals, Asahikasei-pharma, KyowaKirin, Chugai pharmaceutical. T.I. has received research funding from AsahiKasei Pharma, Nippon Shinyaku Co., Ltd. K.F. has received honoraria from Janssen Pharma. J. Kanda has received research funding from Eisai and MSD; has received honoraria from Amgen, Jannsen, Novartis, Abbvie, Daiichi Sankyo, Asahikasei. T. Kobayashi has received research funding from Novartis, Pfizer Japan Inc.; has received honoraria from Novartis and Otsuka. N.H. has received honoraria from Abbvie. T.Y. has received research funding from Otsuka, Pfizer, Abbie, Astellas, Daiichi Sankyo, Solasia Pharma, Sumitomo, Nihon-Shinyaku, Janssen, JCR Pharma, Bristol-Myers-Squibb; has received honoraria from Ono Pharmaceutical, Pfizer, Chugai, Nihon-Shinyaku, Abbvie, Sanofi. T. Kondo has received research funding from Yahoo Japan Foundation; has received honoraria from Pfizer Japan Inc., Otsuka Pharmaceutical, Novartis Pharma KK. K.K. has received research funding from Daiichi-Sankyo and Eisai; has received honoraria from Janssen, AstraZeneca KK, Abbvie. C.Y. has received research funding from Bristol-Myers Squibb; has received honoraria from Novartis, Pfizer, Janssen, Chugai pharmaceutical, Ono Pharmaceutical, Otsuka Pharmaceutical, Abbvie, Nippon Shinyaku, Takeda Pharmaceutical, Bristol-Myers Squibb. A.G. has received research funding from Eisai, Ono Pharmaceutical, Taiho Pharmaceutical, Takeda Pharmaceutical, Nippon Shinyaku, Chugai Pharmaceutical, MSD, Otsuka Pharmaceutical, Sumitomo Dainippon Pharma, Nippon Shinyaku, Bayer Yakuhin, Daiichi-Sankyo, Nihon Pharmaceutical; has received honoraria from Novartis, Alexion Pharmaceuticals, Eisai, Ono Pharmaceutical, Taiho Pharmaceutical, Takeda Pharmaceutical, Nippon Shinyaku, Chugai Pharmaceutical, Otsuka Pharmaceutical, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Nihon Pharmaceutical, Kyowa Kirin, Janssen Pharmaceutical, Pfizer, Sanofi, PharmaEssentia. K.Y. has received research funding from Genmab/IQIVA, Yakult; has received honoraria from Abbvie, Chugai, Eisai, HUYA/IQIVA, Janssen, Meiji Seika Pharma, Micron/Daiichi Sankyo, Takeda. J.Kuroda is a consultant for Janssen Pharmaceutical, Abbvie, Pfizer, BeiGene, and Bristol-Myers Squibb (BMS), has received research funding from Kyowa Kirin, Chugai Pharmaceutical, Japan Blood Product Organization, Sumitomo Pharmaceutical, Otsuka Pharmaceutical, Asahikasei, and Mochida Pharmaceutical and has received honoraria from Janssen Pharmaceutical, Kyowa Kirin, Chugai Pharmaceutical, Ono Pharmaceutical, Sanofi, BMS, Novartis, Abbvie, Pfizer, and Astellas Pharmaceutical. K.I. has received research funding from Ono Pharmaceutical, Kyowa Kirin; has received honoraria from Daiichi Sankyo, Chugai Pharma, Meiji Seika, Bristol-Myers Squibb Japan, Kyowa Kirin. E.S. has received research funding from Bristol-Myers Squibb; has received honoraria from Novartis, Pfizer, Takeda, Sanofi, Janssen Pharmaceutical. H.H. has received honoraria from Otsuka, Kyowa Kirin, Chugai pharmaceutical, Janssen pharmaceutical, Abbvie. K.T. has received honoraria from Eisai, Janssen, Chugai, Sysmex, Ono, Otsuka, Daiichi Sankyo, and Sanofi. Y.M. has received honoraria from Bristol-Myers Squibb Company, Novartis Pharma KK, Pfizer Japan Inc., Takeda. The remaining authors declare no competing financial interests. Consent to publish: Patients signed informed consent regarding publishing their data. Consent to participate: Informed consent was obtained from all individual participants included in the study. Competing interests: The authors declare no competing interests. Compliance with ethical standards: This study was approved by the Research Ethics Committee of National Cancer Center Hospital East (approval number HM-SCREEN-01; UMIN000035233, HM-SCREEN-02; UMIN000046371), and was conducted in accordance with the Declaration of Helsinki.

Figures

Fig. 1
Fig. 1
Overall survival according to TET2 mutation status. The curves of patients with significant TET2 mutations are indicated using orange lines, whereas those of patients with non-significant TET2 mutations and wild-type TET2 are indicated using blue and green lines, respectively (log-rank test: P = 0.0014)
Fig. 2A
Fig. 2A
Survival analysis based on cytogenetic risk. The curves of patients with significant TET2 mutation (sig) with favorable cytogenetic risk are indicated using orange lines, whereas those of patients with significant TET2 mutations with adverse cytogenetic risk are indicated using red lines. The curves of patients with non-significant TET2 mutations (non-sig) or wild-type (wild) TET2 with favorable cytogenetic risk are indicated using green lines, whereas those of patients with TET2 non-significant mutation or wild-type (wild) TET2 with adverse cytogenetic risk are indicated using blue lines (log-rank test, P < 0.0001)
Fig. 2B
Fig. 2B
Survival analysis according to allo-HSCT for risk of TET2 mutation. The curves of patients with significant TET2 mutation (sig) who underwent allo-HSCT are indicated using red lines, whereas those of patients who did not undergo allo-HSCT are indicated using orange lines. The curves of patients with non-significant TET2 mutations (non-sig) or wild-type (wild) TET2 who underwent allo-HSCT are indicated using green lines, and those of patients who did not undergo allo-HSCT are indicated using blue lines (log-rank test: P < 0.0001)
Fig. 3A
Fig. 3A
Survival analysis according to TET2 mutation. The curves of patients with TET2 mutations are indicated by purple lines, whereas those of patients without TET2 mutations are indicated by blue lines (log-rank test, P = 0.0826)
Fig. 3B
Fig. 3B
Survival analysis according to biallelic TET2 mutation. The curves of patients with biallelic TET2 mutations are indicated by purple lines, whereas those of patients without biallelic TET2 mutations are indicated by blue lines (log-rank test, P = 0.0075)
See this image and copyright information in PMC

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