🧫HEMATOPOIETIC STEM CELL BIOLOGY
Tracking clusterin expression in hematopoietic stem cells reveals their heterogeneous composition across the life span. https://tinyurl.com/tw64ckat
- Clusterin (Clu) expression identifies a distinct subset of age-associated HSCs that are biased toward myeloid/platelet differentiation.
- While Clu⁺ HSCs show enhanced self-renewal capacity, Clu⁻ HSCs maintain a lineage-balanced differentiation, revealing that the shift in HSC composition is a major driver of functional aging in hematopoietic stem cells.
Clusterin expression could be used to track aging-associated changes in HSCs.
ACUTE MYELOID LEUKEMIA (AML)
💡 Single-cell Transcriptional Atlas of Human Hematopoiesis Reveals Genetic and Hierarchy-Based Determinants of Aberrant AML Differentiation. https://tinyurl.com/m7334p6x
- A comprehensive single-cell reference atlas of human hematopoiesis was constructed from ~263,000 bone marrow cells, covering 55 distinct cellular states and providing a robust framework for classifying both healthy and leukemic cells.
- Mapping over 1.2 million cells from 318 leukemia patients revealed 12 recurrent patterns of aberrant differentiation in AML, including unexpected lymphoid- and erythroid-like states that were prognostic—highlighting that disease phenotype depends not only on genetic mutations but also on cellular context.
- Genotype-to-phenotype associations showed that identical genetic drivers can lead to different differentiation trajectories, suggesting distinct cellular origins of leukemia stem cells and indicating that hierarchical cell state mapping refines classification and may guide precision therapies.
💡Enhancer Hijacking Discovery in Acute Myeloid Leukemia by Pyjacker Identifies MNX1 Activation via Deletion 7q. https://tinyurl.com/466z3bzs
- A new computational tool, pyjacker, was developed to systematically detect enhancer hijacking events in acute myeloid leukemia with complex karyotypes (ckAML), revealing MNX1 activation via deletion of chromosome 7q and its association with CDK6 enhancer hijacking in about 1.4% of AML cases.
- Functional validation in a xenograft mouse model demonstrated that MNX1 activation is essential for leukemia cell fitness, underscoring the biological significance of enhancer hijacking in AML pathogenesis.
- The study showcases pyjacker as an effective and user-friendly tool for uncovering structural genomic alterations that drive cancer, paving the way for exploring enhancer hijacking across other tumor types.
💡Deconvoluting clonal and cellular architecture in IDH-mutant acute myeloid leukemia. https://tinyurl.com/4b827ux7
- The study provides a high-resolution, single-cell transcriptional atlas of human IDH‑mutant acute myeloid leukemia (AML), distinguishing stem-like cell populations and inflammatory signatures, revealing how IDH mutations reshape cellular hierarchies in AML .
- It identifies specific clonal and cellular phenotypes associated with IDH mutations, offering insights into cellular subtypes that could serve as potential therapeutic targets or biomarkers.
- The findings underscore the critical role of cellular context (stemness and inflammation) in AML pathogenesis, suggesting that targeting these altered phenotypes may improve precision therapies for IDH‑mutant disease
