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<p>The prognosis of acute myeloid leukemia (AML) with <i>KMT2A</i>::<i>MLLT3</i> rearrangement and <i>MECOM</i> overexpression and/or <i>KRAS</i> mutation is dismal, and the optimal treatment strategy remains unclear. However, to the best of our knowledge, a suitable model (such as a cell line or its xenograft model) for research on this subtype has not been established. We established a novel AML cell line, YCU-AML2, and its xenograft model harboring <i>KMT2A</i>::<i>MLLT3</i> rearrangement, <i>MECOM</i> overexpression, and <i>KRAS</i> G12A mutation. YCU-AML2 xenograft mice models developed AML and mimicked the clinical phenotype of the original patient. YCU-AML2 expressed high sensitivity to MEK inhibitors, such as trametinib and selumetinib. Moreover, YCU-AML2 also exhibited high sensitivity to L-asparaginase with glutaminase activity, perhaps because of its reliance on oxidative phosphorylation via glutaminolysis as its main energy source. We believe that the YCU-AML2 cell line and its xenograft model can serve as models to explore the molecular pathogenesis of high-risk AML with <i>KMT2A</i>::<i>MLLT3</i> rearrangement, <i>MECOM</i> overexpression, and/or <i>KRAS</i> mutation and develop new treatment strategies.</p>

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Establishment of a high-risk pediatric AML-derived cell line YCU-AML2 with genetic and metabolic vulnerabilities

  • 期刊论文

  • 发表日期：

    2025年2月1日

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  • Junji Ikeda,
  • Norio Shiba,
  • Shota Kato,
  • Hiroyoshi Kunimoto,
  • Yusuke Saito,
  • Maiko Sagisaka,
  • Mieko Ito,
  • Hiroaki Goto,
  • Yusuke Okuno,
  • Wataru Nakamura,
  • Masahiro Yoshitomi,
  • Masanobu Takeuchi,
  • Shuichi Ito,
  • Hideaki Nakajima,
  • Motohiro Kato,
  • Shin-Ichi Tsujimoto

摘要

The prognosis of acute myeloid leukemia (AML) with KMT2A::MLLT3 rearrangement and MECOM overexpression and/or KRAS mutation is dismal, and the optimal treatment strategy remains unclear. However, to the best of our knowledge, a suitable model (such as a cell line or its xenograft model) for research on this subtype has not been established. We established a novel AML cell line, YCU-AML2, and its xenograft model harboring KMT2A::MLLT3 rearrangement, MECOM overexpression, and KRAS G12A mutation. YCU-AML2 xenograft mice models developed AML and mimicked the clinical phenotype of the original patient. YCU-AML2 expressed high sensitivity to MEK inhibitors, such as trametinib and selumetinib. Moreover, YCU-AML2 also exhibited high sensitivity to L-asparaginase with glutaminase activity, perhaps because of its reliance on oxidative phosphorylation via glutaminolysis as its main energy source. We believe that the YCU-AML2 cell line and its xenograft model can serve as models to explore the molecular pathogenesis of high-risk AML with KMT2A::MLLT3 rearrangement, MECOM overexpression, and/or KRAS mutation and develop new treatment strategies.