Leukemia· 2026Q1
Serine auxotrophy is a targetable vulnerability driven by PSAT1 suppression in AML
- 1citations
- Q1SCImago
- 2026year
Short summary
A subset of Acute Myeloid Leukemia (AML) is completely dependent on external serine (serine auxotrophy), driven by suppressed PSAT1 enzyme, and responds to dietary serine/glycine restriction.
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Key points
- A subset of human AML cell lines and primary samples are serine auxotrophic, meaning they depend on external serine.
- This auxotrophy is consistently associated with suppressed expression of the serine synthesis enzyme PSAT1.
- Serine auxotrophic AML responded to dietary serine and glycine restriction in vivo.
- Dietary serine/glycine restriction synergized with venetoclax in these AML cells.
- MECOM rearrangement was strongly linked to PSAT1 suppression and serine auxotrophy.
AI-generated from the title and abstract; the full text is not read.
Abstract
Serine metabolism is of growing biologic and therapeutic interest in cancer. Upregulation of the serine synthesis pathway (SSP) can fuel tumor growth, and cancers with this phenotype are often sensitive to. SSP inhibitors. In parallel, dietary restriction of serine and glycine (SG) can suppress some cancers, but the determinants of sensitivity to. this approach are poorly understood. This is especially true in acute myeloid leukemia (AML), where serine metabolism has been less explored. We report that a subset of human AML cell lines and primary samples are completely dependent on external serine, known as serine auxotrophy. These leukemias consistently suppressed the SSP enzyme PSAT1, failed to. synthesize serine, responded to. SG restriction in vivo, and were rescued by restoring PSAT1. We also found that SG restriction synergized with venetoclax in serine auxotrophic AML, and that MECOM rearrangement was strongly associated with PSAT1 suppression and serine auxotrophy. These findings define a metabolically distinct AML subtype and nominate it for targeting by SG restriction.
The authors' abstract, as published at the source. Leukemia, 2026 · DOI ↗
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Field: Hematology
HematologyMedicine