Complementary approaches define the metabolic features that accompany Richter syndrome transformation. Academic Article uri icon

Overview

abstract

  • 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.

publication date

  • April 9, 2025

Research

keywords

  • Cell Transformation, Neoplastic
  • Leukemia, Lymphocytic, Chronic, B-Cell

Identity

PubMed Central ID

  • PMC11982009

Digital Object Identifier (DOI)

  • 10.1007/s00018-025-05670-4

PubMed ID

  • 40204982

Additional Document Info

volume

  • 82

issue

  • 1