{
  "abstract": "The combination of azacitidine and venetoclax (Aza/Ven) is an effective treatment for acute myeloid leukemia (AML); however, biological factors underlying heterogeneous treatment responses across diverse genetic backgrounds remain incompletely defined. We analyzed 97 AML patients treated with Aza/Ven in the prospective HM-SCREEN-Japan 02 study using targeted next-generation sequencing (NGS) of 53 genes, cytogenetic analyses, and clinical variables. Somatic mutations were categorized into type 1 (FLT3, PTPN11, WT1, IDH1/2, NPM1, NRAS) and type 2 (GATA2, KRAS, TP53, RUNX1, STAG2, ASXL1, ZRSR2, TET2) groups based on a previously proposed framework describing clonal characteristics. Complete remission (CR) or CR with incomplete hematologic recovery (CRi) was achieved in 53.8%, 52.1%, and 50.0% of patients treated in the first-, second-, and ≥third-line settings, respectively. Among 53 first-line patients with pre-treatment NGS data, type 1–only mutations were more frequently observed in responders (CR/CRi 72%), whereas type 2–only mutations were enriched in non-responders (CR/CRi 33%). In the first-line setting, achievement of CR/CRi following Aza/Ven was associated with improved overall survival. In addition, an exploratory mathematical model integrating baseline clinical variables demonstrated strong discriminatory performance for treatment response, including in cases without established prognostic mutations. In conclusion, Aza/Ven demonstrated consistent clinical activity across treatment lines in this real-world cohort. Mutational patterns classified by a type 1/type 2 framework were associated with differential response patterns in the first-line setting. Integrative modeling approaches may support the interpretation of response heterogeneity, particularly in genetically uninformative AML.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Hematology and Oncology, The University of Osaka Graduate School of Medicine, Suita, Osaka, Japan",
    "Department of Hematology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan",
    "Division of Integrated Research Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Chiba, Japan",
    "Department of Hematology, Saga-ken Medical Centre Koseikan, Kasemachi, Saga, Japan",
    "Division of Hematology, Japanese Red Cross Narita Hospital, Narita, Chiba, Japan",
    "Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Kita-ku, Okayama, Japan",
    "Department of Hematology, NTT Medical Center Tokyo, Shinagawa-ku, Tokyo, Japan",
    "Department of Hematology, Nephrology and Rheumatology, Akita University Graduate School of Medicine, Hondo, Akita, Japan",
    "Department of Hematology and Oncology, University of Fukui, Yoshida-gun, Fukui, Japan",
    "Blood Disorders Center, Aiiku Hospital, Sapporo, Hokkaido, Japan",
    "Department of Hematology and Cell Therapy, Aichi Cancer Center, Chikusa-ku, Nagoya, Japan",
    "Division of Hematology and Oncology, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto, Japan"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 15,
  "authors": [
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        0
      ],
      "name": "Tomoaki Ueda"
    },
    {
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        1
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      "name": "Kentaro Fukushima"
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    {
      "affs": [
        2
      ],
      "name": "Sunggi Chi"
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    {
      "affs": [
        3
      ],
      "name": "Hiroshi Haeno"
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    {
      "affs": [
        4
      ],
      "name": "Goichi Yoshimoto"
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    {
      "affs": [
        5
      ],
      "name": "Hironori Arai"
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    {
      "affs": [
        6
      ],
      "name": "Daisuke Ikeda"
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    {
      "affs": [
        7
      ],
      "name": "Motoshi Ichikawa"
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    {
      "affs": [
        8
      ],
      "name": "Naoto Takahashi"
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    {
      "affs": [
        9
      ],
      "name": "Naoko Hosono"
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    {
      "affs": [
        10
      ],
      "name": "Takahiro Yamauchi"
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    {
      "affs": [
        11
      ],
      "name": "Takeshi Kondo"
    },
    {
      "name": "Shigeru Kusumoto"
    },
    {
      "name": "Junya Kuroda"
    },
    {
      "name": "Yosuke Minami"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/awbbz5y0d4bds.bib",
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  "doi": "10.1371/journal.pone.0357898",
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  "published": "2026-10-01",
  "publisher": "Public Library of Science",
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  "title": "Genomic and clinical determinants of response to Azacitidine plus venetoclax in acute myeloid leukemia: Results from the HM-SCREEN-Japan 02 study",
  "title_text": "Genomic and clinical determinants of response to Azacitidine plus venetoclax in acute myeloid leukemia: Results from the HM-SCREEN-Japan 02 study",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:37Z",
  "url": "https://research.draconitic.com/paper/awbbz5y0d4bds",
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