{
  "id": 3529271,
  "title": "A PTBP1-CDC42 splicing axis regulates leukemia growth and venetoclax sensitivity in acute myeloid leukemia",
  "url": "https://urgent.news/2026/08/26/a-ptbp1-cdc42-splicing-axis-regulates-leukemia-growth-and-venetoclax",
  "topic": "science",
  "section": "Science",
  "published": "2026-08-26T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.08.25.745954v1?rss=1"
  },
  "original_language": "en",
  "account": "Acute myeloid leukemia (AML) is a deadly form of blood cancer with high relapse rates and poor outcomes, particularly in elderly or unfit patients who cannot handle intensive chemotherapy. Venetoclax, a BCL2 inhibitor, has shown promise in improving initial responses in high-risk AML patients, but relapses are almost always inevitable, emphasizing the need for new treatment options. Researchers have now discovered that the RNA-binding protein PTBP1 plays a crucial role in AML, and its depletion hampers leukemic growth both in laboratory tests and animal models. This reduction in growth is linked to widespread changes in splicing and a global slowdown in protein synthesis.\n\nThrough a comprehensive analysis of gene expression and RNA binding, scientists found that PTBP1 controls a splicing program related to Rho GTPase signaling, with CDC42 being a crucial downstream target. When PTBP1 is lost, there is a shift in splicing from CDC42-v1 to CDC42-v2, resulting in diminished GTPase activity and inhibited protein synthesis. Pharmacological blockade of CDC42 specifically triggers cell death in AML cells without harming healthy blood-forming cells. Furthermore, inhibiting CDC42 significantly boosts the effectiveness of venetoclax in treating AML.\n\nThese findings highlight PTBP1 as a vital regulator of AML cell survival and uncover a potential therapeutic combination that takes advantage of AML's reliance on the PTBP1-CDC42 signaling pathway to improve the performance of venetoclax-based treatments.",
  "summary": "Acute myeloid leukemia (AML) is an aggressive blood cancer characterized by high rates of relapse and poor outcomes, especially in elderly or unfit patients, who cannot tolerate intensive chemotherapy. While the BCL2 inhibitor venetoclax has improved initial responses in this high-risk population, relapses remain nearly universal, highlighting the need for novel therapeutic strategies. Here, we…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}