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Updated: Dec 1, 2025

Flow Cytometry to Estimate Leukemia Stem Cells in Primary Acute Myeloid Leukemia and in Patient-derived-xenografts, at Diagnosis and Follow Up
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Targeting LSCs: Peeling Back the Curtain on the Metabolic Complexities of AML

Tian Y Zhang1, Ravindra Majeti1

  • 1Department of Medicine, Division of Hematology, Cancer Institute, and Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.

Cell Stem Cell
|November 6, 2020
PubMed

Insights

Chemoresistant leukemia stem cells (LSCs) cause relapse in acute myeloid leukemia (AML). A new study reveals that targeting nicotinamide metabolism can overcome venetoclax resistance in AML LSCs.

Area of Science:

  • Hematology
  • Cancer Biology
  • Stem Cell Biology

Background:

  • Acute myeloid leukemia (AML) often relapses due to persistent, chemoresistant leukemia stem cells (LSCs).
  • Venetoclax is a promising therapy, but resistance in LSCs limits its long-term efficacy.
  • Understanding resistance mechanisms is crucial for improving AML treatment outcomes.

Purpose of the Study:

  • To identify novel therapeutic targets for overcoming venetoclax resistance in AML LSCs.
  • To elucidate the role of metabolic pathways in LSC survival and drug resistance.

Main Methods:

  • Analysis of LSC populations in relapsed and refractory AML.
  • Investigating the impact of modulating nicotinamide metabolism on LSC viability and venetoclax sensitivity.

Main Results:

  • Jones et al. identified nicotinamide metabolism as a key mechanism driving venetoclax resistance in AML LSCs.
  • Targeting this metabolic pathway sensitized resistant LSCs to venetoclax treatment.
  • This suggests a novel strategy to eliminate persistent LSCs.

Conclusions:

  • Nicotinamide metabolism represents a druggable target to overcome venetoclax resistance in AML.
  • Targeting LSC metabolism could be a promising approach for treating relapsed and refractory AML.
  • This finding offers a potential new avenue for improving patient outcomes in AML.

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