# Ribosomal protein control of hematopoietic stem cell transformation through regulation of metabolism

## TL;DR

This study shows that reduced RPL22 ribosomal protein in blood stem cells leads to leukemia by changing fat metabolism and increasing stem cell self-renewal.

## Contribution

The study reveals a novel mechanism where Rpl22 regulates leukemia through lipid metabolism, not protein synthesis.

## Key findings

- Reduced RPL22 is linked to worse outcomes in MDS and AML patients.
- Rpl22 deficiency causes increased fatty acid oxidation and stemness in leukemia.
- Leukemia survival in Rpl22-deficient mice depends on lipid synthesis promoted by Lin28b.

## Abstract

We report here that expression of the ribosomal protein RPL22 is frequently reduced in human myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML), and reduced RPL22 expression is associated with worse outcomes. Mice null for Rpl22 display characteristics of an MDS-like syndrome and develop leukemia at an accelerated rate. Rpl22-deficient mice also display enhanced hematopoietic stem cell (HSC) self-renewal and obstructed differentiation potential, which arises not from reduced protein synthesis but from altered metabolism, including increased fatty acid oxidation (FAO) and a striking induction of the stemness factor Lin28b in the resulting leukemia. Lin28b promotes a substantial increase in lipid content, upon which the survival of Rpl22-deficient leukemias depends. Altogether, these findings reveal that Rpl22 insufficiency enhances the leukemia potential of HSCs through regulation of FAO and promotes leukemogenesis through Lin28b promotion of lipid synthesis.

Harris et al. demonstrate that insufficiency of the ribosomal protein Rpl22 controls the transformation potential of hematopoietic stem cells (HSCs) not by altering protein synthesis but instead through regulating lipid metabolism, including both fatty acid oxidation and triglyceride synthesis.