Chemotherapy Induces Senescence-Like Resilient Cells Capable of Initiating AML Recurrence.

Area of Science:

• Oncology
• Cell Biology
• Hematology

Background:

• Acute myeloid leukemia (AML) frequently relapses after chemotherapy.
• The mechanisms driving AML reemergence remain incompletely understood.

Purpose of the Study:

• To investigate the cellular mechanisms underlying AML relapse after chemotherapy.
• To identify potential therapeutic targets to prevent AML recurrence.

Main Methods:

• Primary AML cells treated with chemotherapy *in vitro* and *in vivo*.
• Single-cell RNA sequencing to analyze cellular changes.
• Assessment of leukemia stem cell populations and their function.

Main Results:

• Chemotherapy induces a transient senescence-like phenotype in AML cells.
• This state involves specific transcriptional programs and transient depletion of leukemia stem cells.
• Senescence-like AML cells exhibit enhanced colony-forming and engraftment potential.
• ATR signaling is critical for this senescence-like phenotype and AML cell persistence.

Conclusions:

• AML relapse is facilitated by a chemotherapy-induced senescence-like resilience phenotype.
• This phenotype enhances the survival and repopulating capacity of AML cells, irrespective of stem cell status.
• Targeting ATR may represent a therapeutic strategy to prevent AML relapse.