Leukemic stem cell (LSC)–targeted therapies remain a significant unmet need in acute myeloid leukemia (AML). Vujovic, de Rooij et al. used an LSC-focused in vivo CRISPR screen to unveil widespread RNA-binding protein (RBP) dependencies in LSCs including top hit ELAVL1. Genetic and pharmacological inhibition of ELAVL1 significantly impaired leukemic propagation and LSC function while relatively sparing hematopoietic stem cells. Integrative multi-omics analyses revealed posttranscriptional enforcement of LSC-supportive mitochondrial metabolism underpinning ELAVL1 function. This study uncovers novel RBP dependencies unique to LSCs and demonstrates ELAVL1 to be an LSC-specific vulnerability with clinical relevance.

See article, p. 180.

In classic Hodgkin lymphoma (cHL), malignant cells—called Reed Sternberg (HRS) cells—make up only a minority of the tumor. Thus, cell purification is crucial to study cHL genome alterations. Guilino-Roth et al. presented a comprehensive landscape of mutations, copy number, and structural variants of sorted HRS cells and matched normal tissue in cHL obtained...

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