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<p>Ten-eleven translocation-2 (<i>TET2</i>) gene mutations are observed in 12–20% of adult patients with acute myeloid leukemia (AML). The prognostic impact of <i>TET2</i> 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 <i>TET2</i> 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 <i>TET2</i> mutations, with a particularly detrimental prognosis in the patients. Thirty-five patients with <i>TET2</i> ‘significant’ mutations were identified (26 with frameshift mutations and nine with nonsense mutations). The proportion of patients with <i>TET2</i> mutations was 31.7% (10.6% and 21.1% in the <i>TET2</i> significant and non-significant mutation groups). The <i>TET2</i> significant mutation group had a shorter OS than the <i>TET2</i> non-significant mutation or wild-type <i>TET2</i> group (median: 15.9 vs. 35.0 vs. 25.9 months). Regarding the response to chemotherapy according to <i>TET2</i> status, the complete response (CR) or CR with incomplete count recovery rate was 37.1% in the <i>TET2</i> 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 <i>TET2</i> non-significant mutation or wild-type <i>TET2</i> group; however, allo-HSCT did not affect prognosis in the <i>TET2</i> significant mutation group. This study indicates that certain <i>TET2</i> mutations in patients with AML may have detrimental effects.&#xa0;</p>

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

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  • 发表日期：

    2025年1月1日

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  • Satoshi Iyama,
  • SungGi Chi,
  • Masashi Idogawa,
  • Takayuki Ikezoe,
  • Kentaro Fukushima,
  • Yoshikazu Utsu,
  • Junya Kanda,
  • Goichi Yoshimoto,
  • Takahiro Kobayashi,
  • Naoko Hosono,
  • Takahiro Yamauchi,
  • Takeshi Kondo,
  • Yukinori Nakamura,
  • Kensuke Kojima,
  • Chikashi Yoshida,
  • Akihiko Gotoh,
  • Kazuhito Yamamoto,
  • Junya Kuroda,
  • Kenji Ishitsuka,
  • Emiko Sakaida,
  • Hiroto Horiguchi,
  • Kohichi Takada,
  • Hirofumi Ohnishi,
  • Masayoshi Kobune,
  • Yosuke Minami

摘要

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.