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This research aims to identify leukemic stem cell subtypes that contribute to venetoclax resistance in AML and explore potential targeted therapies.

May 11, 2026Cell stem cell3 citationsOpen Access

Leukemic stem cell subtypes determine venetoclax resistance and therapeutic vulnerabilities in AML

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AWAlexander Waclawiczek ALAino‐Maija Leppä SRSimon Renders

Key Points

This research aims to identify leukemic stem cell subtypes that contribute to venetoclax resistance in AML and explore potential targeted therapies.
Subtyped leukemic stem cells to assess resistance mechanisms to venetoclax.
Evaluated responses of specific LSC types to various therapeutic agents such as BCL-xL and MEK1/2 inhibitors.
Identified four distinct LSC types with unique vulnerabilities.
MEP-LSCs showed resistance to venetoclax but responsiveness to BCL-xL inhibitors.
MoDe-LSCs were sensitive to MEK1/2 inhibition.

Abstract

monocytic AMLs, drive venetoclax resistance. LSC subtyping improves genetic risk stratification and provides subtype-specific therapies: venetoclax-resistant MEP-LSCs respond to BCL-xL inhibitors, whereas MoDe-LSCs are sensitive to MEK1/2 inhibition. Our findings reveal four distinct LSC types with unique vulnerabilities and propose biomarker-guided treatment strategies that complement genetic profiling to overcome venetoclax resistance.

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Leukemic stem cell subtypes determine venetoclax resistance and therapeutic vulnerabilities in AML

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