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Related Experiment Video

Updated: Oct 25, 2025

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Pan-PI3Ki targets multiple B-ALL microenvironment interactions that fuel systemic and CNS relapse.

Sarah M Ridge1, Andrew E Whiteley1, Hisayuki Yao1,2

  • 1Department of Medicine, Division of Hematologic Malignancies and Cellular Therapy, Duke University, Durham, NC, USA.

Leukemia & Lymphoma
|August 6, 2021
PubMed
Summary
This summary is machine-generated.

Targeting PI3K isoforms halts growth in B-cell acute lymphoblastic leukemia (B-ALL). Pan-PI3K inhibitors like copanlisib reduce systemic disease and CNS metastasis, showing promise for leukemia treatment.

Keywords:
CNS relapsePI3K inhibitionacute lymphoblastic leukemiachemosensitizationmicroenvironment

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Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Adult acute lymphoblastic leukemia (ALL) frequently relapses, with central nervous system (CNS) metastasis indicating a poor prognosis.
  • Previous research identified PI3Kδ-regulated integrin α6 as a route for ALL CNS metastasis, but B-ALL cells did not rely on PI3Kδ for growth.

Purpose of the Study:

  • To investigate the efficacy of broad PI3K isoform targeting in B-ALL.
  • To explore the vulnerability of B-ALL cells to PI3K inhibitors under cellular stress.
  • To evaluate the potential of pan-PI3K inhibitors (pan-PI3Ki) for B-ALL treatment, including CNS prophylaxis and chemosensitization.

Main Methods:

  • Treatment of B-ALL models with a pan-PI3K inhibitor, copanlisib.
  • Assessment of B-ALL cell growth arrest and systemic disease burden in mice.
  • Investigation of PI3K/Akt-dependent survival pathways activated by cellular stress in B-ALL.
  • Evaluation of copanlisib combined with chemotherapy in reducing systemic disease and CNS metastasis.

Main Results:

  • A single agent pan-PI3Ki, copanlisib, induced growth arrest in B-ALL and reduced systemic disease burden in mice.
  • Cellular stress activates PI3K/Akt survival pathways in B-ALL, making them vulnerable to PI3Kδ and pan-PI3Ki.
  • Combining copanlisib with chemotherapy improved survival, decreased systemic disease, and reduced CNS metastasis.

Conclusions:

  • Broad targeting of PI3K isoforms can induce growth arrest in B-ALL.
  • Pan-PI3Ki, such as copanlisib, demonstrate multifaceted potential for B-ALL CNS prophylaxis, systemic disease control, and chemosensitization.
  • The combination of pan-PI3Ki with chemotherapy offers significant therapeutic benefits for B-ALL patients.