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<p>Richter syndrome (RS) is the transformation of chronic lymphocytic leukemia (CLL) into a high-grade lymphoma with previously unknown metabolic features. Transcriptomic data from primary CLL and RS samples, as well as RS-patient-derived xenografts, highlighted cellular metabolism as one of the most significant differentially expressed processes. Activity assays of key enzymes confirmed the intense metabolic rewiring of RS cells, which is characterized by an elevated rate of Krebs cycle, oxidative phosphorylation, and glutamine metabolism. These pathways were sustained by increased uptake of glucose and glutamine, two critical substrates for these cells. Moreover, RS cells showed activation of anabolic processes that resulted in the synthesis of nucleotides and lipids necessary to support their high proliferation. Exposure to drugs targeting PI3K and NF-kB, two master regulators of cellular metabolism, resulted in the shutdown of ATP production and glycolysis. Overall, these data suggest that metabolic rewiring characterizes the transformation of CLL into RS, presenting new translational opportunities.</p>

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Complementary approaches define the metabolic features that accompany Richter syndrome transformation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月9日

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  • Giulia Omezzolli,
  • Andrea Iannello,
  • Francesco E. Vallone,
  • Lorenzo Brandimarte,
  • Matilde Micillo,
  • Nadia Bertola,
  • Chiara Lavarello,
  • Nicole Grinovero,
  • Giulio Ferrero,
  • Kevin Mellert,
  • Peter Möller,
  • Silvia Bruno,
  • Richard R. Furman,
  • John N. Allan,
  • Andrea Petretto,
  • Silvia Deaglio,
  • Silvia Ravera,
  • Tiziana Vaisitti

摘要

Richter syndrome (RS) is the transformation of chronic lymphocytic leukemia (CLL) into a high-grade lymphoma with previously unknown metabolic features. Transcriptomic data from primary CLL and RS samples, as well as RS-patient-derived xenografts, highlighted cellular metabolism as one of the most significant differentially expressed processes. Activity assays of key enzymes confirmed the intense metabolic rewiring of RS cells, which is characterized by an elevated rate of Krebs cycle, oxidative phosphorylation, and glutamine metabolism. These pathways were sustained by increased uptake of glucose and glutamine, two critical substrates for these cells. Moreover, RS cells showed activation of anabolic processes that resulted in the synthesis of nucleotides and lipids necessary to support their high proliferation. Exposure to drugs targeting PI3K and NF-kB, two master regulators of cellular metabolism, resulted in the shutdown of ATP production and glycolysis. Overall, these data suggest that metabolic rewiring characterizes the transformation of CLL into RS, presenting new translational opportunities.