Metabolic Adaptations To Acute Glucose Uptake Inhibition Converge Upon Mitochondrial Respiration For Leukemia Cell Survival.

One hallmark of cancer is the upregulation and dependency on glucose metabolism to fuel macromolecule biosynthesis and rapid proliferation. Despite significant pre-clinical effort to exploit this pathway, additional mechanistic insights are necessary to prioritize the diversity of metabolic adaptations upon acute loss of glucose metabolism. Here, we investigated a potent small molecule inhibitor to Class I glucose transporters, KL-11743, using glycolytic leukemia cell lines and patient-based model systems.

The crossroads of clonal evolution, differentiation hierarchy and ontogeny in leukemia development.

Transformative technologies to sequence tumor genomes at large scale and single-cell resolution have exposed the repertoire of genetic alterations that are present in leukemia genomes, the timing of their acquisition and patterns of their co-occurrence. In parallel, single-cell multi-omics technologies are allowing us to map the differentiation paths and hierarchical structures of malignant cells and giving us a glimpse into hematopoietic development in prenatal life. We propose that interrogating how the genetic evolution, differentiation hierarchy and ontogeny of malignant myeloid cells intersect with each other, using new experimental systems and multimodal technologies, will fuel the next generation of research breakthroughs.

Clonal landscape and clinical outcomes of telomere biology disorders: somatic rescue and cancer mutations.

Telomere biology disorders (TBDs), caused by pathogenic germ line variants in telomere-related genes, present with multiorgan disease and a predisposition to cancer. Clonal hematopoiesis (CH) as a marker of cancer development and survival in TBDs is poorly understood. Here, we characterized the clonal landscape of a large cohort of 207 patients with TBD with a broad range of age and phenotype.