Related Experiment Video

Updated: Jan 22, 2026

Using Caenorhabditis elegans as a Model System to Study Protein Homeostasis in a Multicellular Organism
12:38

Using Caenorhabditis elegans as a Model System to Study Protein Homeostasis in a Multicellular Organism

Published on: December 18, 2013

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Mitochondrial Homeostasis in AML and Gasping for Response in Resistance to BCL2 Blockade

Michael R Savona1,2, Jeffrey C Rathmell2,3

  • 1Division of Hematology & Oncology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee. michael.savona@vanderbilt.edu.

Cancer Discovery
|July 3, 2019
PubMed

Insights

Researchers identified new ways to overcome resistance to BCL2 inhibitors in acute myeloid leukemia. Large CRISPR screens revealed targetable vulnerabilities in cell signaling and metabolism for resistant leukemia cells.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Resistance to BCL2 inhibition presents a significant hurdle in treating acute myeloid leukemia (AML).
  • Identifying mechanisms of resistance is crucial for developing effective therapeutic strategies.

Purpose of the Study:

  • To uncover targetable vulnerabilities that confer resistance to BCL2 inhibition in AML.
  • To identify novel therapeutic strategies for overcoming BCL2 inhibitor resistance in AML.

Main Methods:

  • Utilized large-scale, unbiased loss-of-function CRISPR/Cas9 screening.
  • Applied these screens to AML models exhibiting resistance to BCL2 inhibitors.

Main Results:

  • Discovered critical roles of specific cell signaling pathways in mediating resistance.
  • Identified key metabolic liabilities that can be targeted in resistant AML.
  • Two independent laboratories converged on similar targetable vulnerabilities.

Conclusions:

  • Unbiased CRISPR screens are powerful tools for dissecting complex resistance mechanisms in AML.
  • Targeting identified cell signaling and metabolic vulnerabilities offers promising therapeutic avenues for BCL2-refractory AML.

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