Abnormal nuclear morphology is a hallmark of most cancers, widely used in cancer diagnosis. In this paper, the authors discover that aberrant nuclear shape in blood cancers is caused by the deletion of a gene called lamin B1. Lamins are proteins that line the inside of the nucleus and are mutated in inherited disorders, such as progeria. They show that lamin B1 deletion causes changes in stem cell function, nuclear shape, and leukemia progression. They discover that the lamin B1 gene is responsible for the abnormal nuclei that have puzzled and helped pathologists recognize cancers over the past century.