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Signaling Pathways in Leukemic Stem Cells

Lindsay M Gurska1,2, Kristina Ames1,2, Kira Gritsman3,4,5

  • 1Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York, USA.

Advances in Experimental Medicine and Biology
|July 25, 2019
PubMed

Insights

Hematopoietic stem cells (HSCs) and leukemic stem cells (LSCs) share signaling pathways. This review highlights differences in these pathways, like PI3K/AKT/mTOR, WNT, NOTCH, and TGFβ, to identify LSC-specific therapeutic targets.

Area of Science:

  • Cellular biology
  • Molecular oncology
  • Stem cell research

Background:

  • Hematopoietic stem cells (HSCs) and leukemic stem cells (LSCs) share common signaling pathways essential for their survival.
  • Understanding these shared pathways is crucial for developing targeted therapies against leukemia.

Purpose of the Study:

  • To review key signaling pathways, including PI3K/AKT/mTOR, WNT/β-catenin, NOTCH, and TGFβ, in both HSCs and LSCs.
  • To identify differences in pathway function between HSCs and LSCs to pinpoint LSC-specific therapeutic vulnerabilities.
  • To explore potential crosstalk between signaling pathways impacting LSC function.

Main Methods:

  • Literature review focusing on signaling pathways in HSCs and LSCs.
  • Comparative analysis of pathway regulation and function in normal versus malignant stem cells.
  • Identification of therapeutic targets based on pathway dysregulation in LSCs.

Main Results:

  • The PI3K/AKT/mTOR pathway is a central focus, with its regulators and effectors playing critical roles in both HSCs and LSCs.
  • Distinct roles of WNT/β-catenin, NOTCH, and TGFβ pathways in LSC maintenance and survival compared to HSCs were identified.
  • Significant crosstalk between various signaling pathways influencing LSC behavior was highlighted.

Conclusions:

  • Targeting shared signaling pathways with an emphasis on their differential roles in LSCs presents a promising strategy for leukemia therapy.
  • Understanding pathway crosstalk is essential for developing effective and specific LSC-targeting treatments.
  • Further research into these pathways could lead to novel therapeutic interventions for hematologic malignancies.

Keywords:
AktFOXOHematopoietic stem cellLeukemic stem cellNOTCHPI3KSignalingTGFβWNTmTORβ-Catenin

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